KR20230145111A - Hydroxyheterocycloalkane-carbamoyl derivatives - Google Patents

Hydroxyheterocycloalkane-carbamoyl derivatives Download PDF

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KR20230145111A
KR20230145111A KR1020237030395A KR20237030395A KR20230145111A KR 20230145111 A KR20230145111 A KR 20230145111A KR 1020237030395 A KR1020237030395 A KR 1020237030395A KR 20237030395 A KR20237030395 A KR 20237030395A KR 20230145111 A KR20230145111 A KR 20230145111A
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pyran
hydroxy
hydroxymethyl
carboxamide
triazol
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마르틴 볼리
욘 가트필트
코리나 그리소스토미
루보스 레멘
크리슈토프 자거
코르넬리아 춤브룬
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이도르시아 파마슈티컬스 리미티드
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4192—1,2,3-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics

Abstract

본 발명은 식 (I) 의 화합물

(식에서 X, Ar 1 , Ar 2 , L, n, m, 및 R 1 은 상세한 설명에서 기술된 바와 같음), 이의 제조, 이의 약학적으로 허용가능한 염, 및 이의 의약으로서의 용도, 하나 이상의 식 (I) 의 화합물을 함유하는 약학적 조성물, 및 특히 이의 갈렉틴-3 저해제로서의 용도에 관한 것이다.The present invention relates to compounds of formula (I)

( wherein _ _ _ _ _ _ _ _ It relates to pharmaceutical compositions containing the compounds of I) and in particular to their use as galectin-3 inhibitors.

Description

히드록시헤테로시클로알칸-카르바모일 유도체Hydroxyheterocycloalkane-carbamoyl derivatives

본 발명은 갈렉틴-3 저해제인 식 (I) 의 화합물 및 천연 리간드에 대한 갈렉틴-3 결합과 관련되는 질환 및 장애의 예방 / 방지 또는 치료에서의 이의 용도에 관한 것이다. 본 발명은 또한 이 화합물의 제조 방법, 하나 이상의 식 (I) 의 화합물을 함유하는 약학적 조성물, 및 갈렉틴-3 저해제로서의 이의 의학적 용도를 포함하는 관련 양태에 관한 것이다. 식 (I) 의 화합물은 특히 단일 작용제로서 또는 하나 이상의 치료제와 조합으로 사용될 수 있다.The present invention relates to compounds of formula (I) which are galectin-3 inhibitors and their use in the prevention/prevention or treatment of diseases and disorders associated with galectin-3 binding to natural ligands. The invention also relates to related aspects, including processes for the preparation of these compounds, pharmaceutical compositions containing at least one compound of formula (I), and their medical use as galectin-3 inhibitors. The compounds of formula (I) can in particular be used as single agents or in combination with one or more therapeutic agents.

갈렉틴은 그들의 특징적인 ~130 개 아미노산 (aa) 탄수화물 인지 도메인 (CRD) 내에서 발견되는 보존된 β-갈락토시드-결합 자리에 기반하는 단백질 패밀리로서 정의된다 (Barondes SH et al., Cell 1994; 76, 597-598). 인간, 마우스 및 랫트 게놈 서열은 하나의 포유류 게놈에서 적어도 16 개의 보존된 갈렉틴 및 갈렉틴-유사 단백질의 존재를 나타낸다 (Leffler H. et al., Glycoconj. J. 2002, 19, 433-440). 지금까지, 3 개의 갈렉틴 서브클래스, 하나의 탄수화물-인식 도메인 (CRD) 을 함유하는 원형 갈렉틴; CRD 에 융합된 프롤린- 및 글리신-풍부 짧은 스트레치의 비정상적 일렬 반복으로 이루어지는 키메라 갈렉틴; 및 링커에 의해 나란히 연결된 2 개의 별개 CRD 를 함유하는 일렬-반복-유형 갈렉틴이 확인되었다 (Zhong X., Clin Exp Pharmacol Physiol. 2019; 46:197-203). 갈렉틴이 이가 또는 다가로 결합할 수 있으므로, 이들은 예를 들어 세포 표면 글리코컨쥬게이트에 가교결합하여 세포 신호전달 사건을 촉발시킬 수 있다. 이러한 메커니즘을 통해, 갈렉틴은 다양한 생물학적 과정을 조절한다 (Sundblad V. et al., Histol Histopathol 2011; 26: 247-265).Galectins are defined as a family of proteins based on a conserved β-galactoside-binding site found within their characteristic ~130 amino acid (aa) carbohydrate recognition domain (CRD) (Barondes SH et al., Cell 1994 ; 76, 597-598). Human, mouse and rat genome sequences reveal the presence of at least 16 conserved galectins and galectin-like proteins in one mammalian genome (Leffler H. et al., Glycoconj. J. 2002, 19, 433-440) . So far, there are three galectin subclasses: the prototypic galectins, which contain one carbohydrate-recognition domain (CRD); Chimeric galectins consisting of aberrant tandem repeats of proline- and glycine-rich short stretches fused to a CRD; and a tandem-repeat-type galectin containing two distinct CRDs connected side by side by a linker has been identified (Zhong X., Clin Exp Pharmacol Physiol. 2019; 46:197-203). Because galectins can bind divalently or multivalently, they can trigger cell signaling events, for example by cross-linking to cell surface glycoconjugates. Through this mechanism, galectins regulate various biological processes (Sundblad V. et al., Histol Histopathol 2011; 26: 247-265).

갈렉틴 패밀리에서의 유일한 키메라 유형인 갈렉틴-3 (Gal-3) 은 분자량이 32-35 kDa 이며 인간에서 250 개의 아미노산 잔기, 고도로 보존된 CRD 및 비정형 N-말단 도메인 (ND) 으로 이루어진다. 갈렉틴-3 은 고농도 (100 μM) 까지의 단량체이지만 훨씬 더 낮은 농도에서 리간드와 응집할 수 있으며, 이는 아직 완전히 이해되지 않은 올리고머화 메커니즘을 통해 그의 N-말단 비-CRD 부위에 의해 촉진된다 (Johannes, L. et al., Journal of Cell Science 2018; 131, jcs208884).Galectin-3 (Gal-3), the only chimeric type in the galectin family, has a molecular weight of 32-35 kDa and consists of 250 amino acid residues in humans, a highly conserved CRD and an atypical N-terminal domain (ND). Galectin-3 is monomeric up to high concentrations (100 μM) but can aggregate with ligands at much lower concentrations, which is promoted by its N-terminal non-CRD region through an oligomerization mechanism that is not yet fully understood ( Johannes, L. et al., Journal of Cell Science 2018; 131, jcs208884).

Gal-3 은 체내에 널리 분포되어 있으나, 발현 수준은 상이한 기관에 따라 가변적이다. 그의 세포외 또는 세포내 국부화에 따라, 이는 면역조절, 숙주-병원체 상호작용, 혈관형성, 세포 이동, 상처 치유 및 세포자멸사를 포함하는 광범위한 생물학적 기능을 나타낼 수 있다 (Sundblad V. et al., Histol Histopathol 2011; 26: 247-265). Gal-3 은 다수의 인간 종양 및 세포 유형, 예컨대 골수성 세포, 염증성 세포 (대식세포, 비만 세포, 호중구, T 세포, 호산구 등), 섬유아세포 및 심근세포에서 고도로 발현되는데 (Zhong X. et al., Clin Exp Pharmacol Physiol. 2019; 46:197-203), 이는 Gal-3 이 염증 및 섬유증 과정의 조절에 관여한다는 것을 나타낸다 (Henderson NC. Et al., Immunological Reviews 2009; 230: 160-171; Sano H. et al., J Immunol.　2000; 165(4):2156-64). 또한, Gal-3 단백질 발현 수준은 신생물 및 염증과 같은 특정 병리학적 조건 하에 상향조절된다 (Chiariotti L. et al., Glycoconjugate Journal 2004 19, 441-449; Farhad M. et al., OncoImmunology 2018, 7:6, e1434467).Gal-3 is widely distributed in the body, but expression levels are variable in different organs. Depending on its extracellular or intracellular localization, it can exhibit a wide range of biological functions, including immunomodulation, host-pathogen interactions, angiogenesis, cell migration, wound healing and apoptosis (Sundblad V. et al., Histol Histopathol 2011; 26: 247-265). Gal-3 is highly expressed in multiple human tumors and cell types, such as myeloid cells, inflammatory cells (macrophages, mast cells, neutrophils, T cells, eosinophils, etc.), fibroblasts, and cardiomyocytes (Zhong X. et al. , Clin Exp Pharmacol Physiol. 2019; 46:197-203), indicating that Gal-3 is involved in the regulation of inflammatory and fibrotic processes (Henderson NC. Et al., Immunological Reviews 2009; 230: 160-171; Sano H. et al., J Immunol.　2000;165(4):2156-64). Additionally, Gal-3 protein expression levels are upregulated under certain pathological conditions such as neoplasia and inflammation (Chiariotti L. et al., Glycoconjugate Journal 2004 19, 441-449; Farhad M. et al., OncoImmunology 2018, 7:6, e1434467).

염증성 / 자가면역 질환, 예컨대 천식 (Gao P. et al. Respir Res. 2013, 14:136; Rao SP et al. Front Med (Lausanne) 2017; 4:68), 류마티스 관절염, 다발성 경화증, 당뇨병, 판상 건선 (Lacina L. et al. Folia Biol (Praha) 2006; 52(1-2):10-5), 아토피성 피부염 (Saegusa J. et al. Am J Pathol. 2009, 174(3):922-31), 자궁내막증 (Noel JC et al. Appl Immunohistochem Mol Morphol. 2011 19(3):253-7) 또는 바이러스성 뇌염 (Liu FT et al., Ann N Y Acad Sci. 2012; 1253:80-91; Henderson NC, et al., Immunol Rev. 2009;230(1):160-71; Li P et al.,Cell 2016; 167:973-984) 의 발생에서 Gal-3 의 기능적 관련을 지지하는 다수의 증거가 존재한다. 최근 Gal-3 은 만성 염증 및 기관 섬유생성 발달, 예를 들어 간 (Henderson NC et al., PNAS 2006; 103: 5060-5065; Hsu DK et al. Int J Cancer. 1999, 81(4):519-26), 신장 (Henderson NC et al., Am. J. Pathol. 2008; 172:288-298; Dang Z. et al. Transplantation. 2012, 93(5):477-84), 폐 (Mackinnon AC et al., Am. J. Respir. Crit. Care Med 2012, 185: 537-546; Nishi Y. et al. Allergol Int. 2007, 56(1):57-65), 심장 (Thandavarayan RA et al. Biochem Pharmacol. 2008, 75(9):1797-806; Sharma U. et al. Am J Physiol Heart Circ Physiol. 2008; 294(3):H1226-32) 뿐만 아니라 신경계 (Burguillos MA et al. Cell Rep. 2015, 10(9):1626-1638) 및 각막 혈관신생 (Chen WS. Et al., Investigative Ophthalmology & Visual Science 2017, Vol.58, 9-20) 에서 핵심 참가자로 부각되었다. 또한, Gal-3 은 켈로이드 조직의 진피 비후 (Arciniegas E. et al., The American Journal of dermatopathology 2019; 41(3):193-204) 및 전신 경화증 (SSc), 특히 이러한 병상에서 관찰되는 피부 섬유증 및 증식성 혈관병증 (Taniguchi T. et al. J Rheumatol. 2012, 39(3):539-44) 과 연관되는 것으로 발견되었다. Gal-3 은 만성 신장 질환 (CKD) 연관-신부전을 앓고 있는 환자, 및 특히 당뇨병에 걸린 환자에서 상향조절되는 것으로 발견되었다. 흥미롭게도, 이 환자 집단으로부터 수득한 데이터는 사구체에서의 Gal-3 상향조절과 관찰된 요단백 배출 사이의 상관관계를 나타내었다 (Kikuchi Y. et al. Nephrol Dial Transplant. 2004,19(3):602-7). 또한, 2018 년의 최근 예상 연구는 특히 고혈압을 앓는 집단 중에서, 더 높은 Gal-3 혈장 수준이 사건 CKD 발생 위험의 상승과 연관된다는 것을 입증했다 (Rebholz CM. et al. Kidney Int. 2018 Jan; 93(1): 252-259). Gal-3 은 심혈관 질환 (Zhong X. et al. Clin Exp Pharmacol Physiol. 2019, 46(3):197-203), 예컨대 죽상동맥경화증 (Nachtigal M. et al. Am J Pathol. 1998; 152(5):1199-208), 관상 동맥 질환 (Falcone C. et al. Int J Immunopathol Pharmacol 2011, 24(4):905-13), 심부전 및 혈전증 (Nachtigal M. et al., Am J Pathol. 1998; 152(5):1199-208; Gehlken C. et al., Heart Fail Clin. 2018,14(1):75-92; DeRoo EP. et al., Blood. 2015, 125(11):1813-21) 에서 매우 상승된다. Gal-3 혈액 농도는 비만 및 당뇨병 환자에서 증가하며 미세혈관 및 거대혈관 합병증 (예컨대 심부전, 신장병증/망막병증, 말초 동맥 질환, 뇌혈관 사건 또는 심근 경색) 에 대한 더 높은 위험성과 연관된다 (Qi-hui-Jin et al. Chin Med J (Engl). 2013,126(11):2109-15). Gal-3 은 종양형성, 암 진행 및 전이에 영향을 주며 (Vuong L. et al., Cancer Res 2019 (79) (7) 1480-1492), 미세 종양 환경 내에서 작용하여 면역 감시를 저해함으로써 전 (pro)-종양 인자로서 역할하는 것으로 나타났다 (Ruvolo PP. et al. Biochim Biophys Acta. 2016 Mar,1863(3):427-437; Farhad M. et al. Oncoimmunology 2018 Feb 20;7(6):e1434467). 높은 수준의 Gal-3 을 발현하는 암 중에서 갑상선, 중추신경계, 혀, 유방, 위 시스템, 두경부 편평 세포, 췌장, 방광, 신장, 간, 부갑상선, 침샘 뿐만 아니라 림프종, 암종, 비-소세포 폐암, 흑색종 및 신경아세포종에 영향을 주는 것들이 발견된다 (Sciacchitano S. et al. Int J Mol Sci 2018 Jan 26,19(2):379).Inflammatory/autoimmune diseases, such as asthma (Gao P. et al. Respir Res. 2013, 14:136; Rao SP et al. Front Med (Lausanne) 2017; 4:68), rheumatoid arthritis, multiple sclerosis, diabetes, plaque Psoriasis (Lacina L. et al. Folia Biol (Praha) 2006; 52(1-2):10-5), atopic dermatitis (Saegusa J. et al. Am J Pathol. 2009, 174(3):922- 31), endometriosis (Noel JC et al. Appl Immunohistochem Mol Morphol. 2011 19(3):253-7) or viral encephalitis (Liu FT et al., Ann N Y Acad Sci. 2012; 1253:80-91; Henderson NC, et al., Immunol Rev. 2009;230(1):160-71; Li P et al.,Cell 2016;167:973-984) A number of studies support the functional involvement of Gal-3 in the development of The evidence exists. Recently, Gal-3 has been implicated in chronic inflammation and organ fibrotic development, e.g. in the liver (Henderson NC et al., PNAS 2006; 103: 5060-5065; Hsu DK et al. Int J Cancer. 1999, 81(4):519 -26), kidney (Henderson NC et al., Am. J. Pathol. 2008; 172:288-298; Dang Z. et al. Transplantation. 2012, 93(5):477-84), lung (Mackinnon AC et al., Am. J. Respir. Crit. Care Med 2012, 185: 537-546; Nishi Y. et al. Allergol Int. 2007, 56(1):57-65), heart (Thandavarayan RA et al. Biochem Pharmacol. 2008, 75(9):1797-806; Sharma U. et al. Am J Physiol Heart Circ Physiol. 2008; 294(3):H1226-32) as well as the nervous system (Burguillos MA et al. Cell Rep. 2015, 10(9):1626-1638) and corneal neovascularization (Chen WS. Et al., Investigative Ophthalmology & Visual Science 2017, Vol.58, 9-20). Additionally, Gal-3 is involved in dermal thickening of keloid tissue (Arciniegas E. et al., The American Journal of dermatopathology 2019; 41(3):193-204) and systemic sclerosis (SSc), especially the skin fibrosis observed in these conditions. and proliferative angiopathy (Taniguchi T. et al. J Rheumatol. 2012, 39(3):539-44). Gal-3 has been found to be upregulated in patients suffering from chronic kidney disease (CKD) associated-renal failure, and especially in patients with diabetes. Interestingly, data obtained from this patient population showed a correlation between Gal-3 upregulation in glomeruli and observed urinary protein excretion (Kikuchi Y. et al. Nephrol Dial Transplant. 2004,19(3): 602-7). Additionally, a recent prospective study from 2018 demonstrated that higher Gal-3 plasma levels are associated with an elevated risk of developing incident CKD, especially among populations with hypertension (Rebholz CM. et al. Kidney Int. 2018 Jan; 93 (1): 252-259). Gal-3 is involved in cardiovascular diseases (Zhong ):1199-208), coronary artery disease (Falcone C. et al. Int J Immunopathol Pharmacol 2011, 24(4):905-13), heart failure and thrombosis (Nachtigal M. et al., Am J Pathol. 1998; 152(5):1199-208; Gehlken C. et al., Heart Fail Clin. 2018,14(1):75-92; DeRoo EP. et al., Blood. 2015, 125(11):1813-21 ) rises significantly. Gal-3 blood concentrations are increased in obese and diabetic patients and are associated with a higher risk for microvascular and macrovascular complications (e.g. heart failure, nephropathy/retinopathy, peripheral artery disease, cerebrovascular events or myocardial infarction) (Qi -hui-Jin et al. Chin Med J (Engl). 2013,126(11):2109-15). Gal-3 affects tumorigenesis, cancer progression, and metastasis (Vuong L. et al., Cancer Res 2019 (79) (7) 1480-1492), and acts within the microtumoral environment to promote metastasis by inhibiting immune surveillance. (pro)-Showed to act as a tumor factor (Ruvolo PP. et al. Biochim Biophys Acta. 2016 Mar,1863(3):427-437; Farhad M. et al. Oncoimmunology 2018 Feb 20;7(6): e1434467). Among cancers expressing high levels of Gal-3, thyroid, central nervous system, tongue, breast, gastric system, head and neck squamous cell, pancreas, bladder, kidney, liver, parathyroid, and salivary glands, as well as lymphoma, carcinoma, non-small cell lung cancer, and melanoma. Those affecting species and neuroblastoma are found (Sciacchitano S. et al. Int J Mol Sci 2018 Jan 26,19(2):379).

또한, Gal-3 저해는 아마도 항-염증 효과로 인해 COVID-19 (Caniglia JL et al.PeerJ 2020, 8:e9392) 및 인플루엔자 H5N1 (Chen YJ et al. Am. J. Pathol. 2018, 188(4), 1031-1042) 의 치료에 유익한 것으로 제안되었다.Additionally, Gal-3 inhibition may be effective against COVID-19 (Caniglia JL et al.PeerJ 2020, 8:e9392) and influenza H5N1 (Chen YJ et al. Am. J. Pathol. 2018, 188(4), possibly due to its anti-inflammatory effects. ), 1031-1042) has been suggested to be beneficial in the treatment of

최근, Gal-3 저해제는 병용 면역요법 (Galectin Therapeutics. Press Release, February 7, 2017) 및 특발성 폐 섬유증 (Galecto Biotech. Press Release, March 10, 2017) 및 NASH 간경변증 (December 05, 2017) 에서 사용시 긍정적인 효과를 갖는 것으로 나타났다. WO20180209276, WO2018209255 및 WO20190890080 은 전신 인슐린 저항성 장애의 치료를 위한 갈렉틴 단백질과의 결합 친화성을 갖는 화합물을 개시하고 있다. 따라서, Gal-3 저해제는 단독으로 또는 다른 치료요법과 조합으로, 기관의 섬유증, 심혈관 질환 및 장애, 급성 신장 손상 및 만성 신장 질환, 간 질환 및 장애, 간질성 폐 질환 및 장애, 안구 질환 및 장애, 세포 증식성 질환 및 암, 염증성 및 자가면역 질환 및 장애, 위장관 질환 및 장애, 췌장 질환 및 장애, 비정상적 혈관형성 관련 질환 및 장애, 뇌 관련 질환 및 장애, 신경병성 통증 및 말초 신경병증, 및 / 또는 이식 거부증과 같은 질환 또는 장애의 예방 또는 치료에 유용할 수 있다.Recently, Gal-3 inhibitors have shown positive results when used in combination immunotherapy (Galectin Therapeutics. Press Release, February 7, 2017) and in idiopathic pulmonary fibrosis (Galecto Biotech. Press Release, March 10, 2017) and NASH cirrhosis (December 05, 2017). It was found to have a phosphorus effect. WO20180209276, WO2018209255 and WO20190890080 disclose compounds with binding affinity to galectin proteins for the treatment of systemic insulin resistance disorders. Thus, Gal-3 inhibitors, alone or in combination with other therapies, can be used to treat organ fibrosis, cardiovascular diseases and disorders, acute kidney injury and chronic kidney disease, liver diseases and disorders, interstitial lung diseases and disorders, and ocular diseases and disorders. , cell proliferative diseases and cancers, inflammatory and autoimmune diseases and disorders, gastrointestinal diseases and disorders, pancreatic diseases and disorders, diseases and disorders associated with abnormal angiogenesis, brain-related diseases and disorders, neuropathic pain and peripheral neuropathy, and / Alternatively, it may be useful for preventing or treating diseases or disorders such as transplant rejection.

여러 공개물 및 특허 출원은 항섬유증화제로서 연구되고 있는 Gal-3 의 합성 저해제를 기재하고 있다 (예를 들어 WO2005113568, WO2005113569, WO2014067986, WO2016120403, US20140099319, WO2019067702, WO2019075045, WO2014078655, WO2020078807, WO2020078808 및 WO2020210308 참조).Several publications and patent applications describe inhibitors of the synthesis of Gal-3, which are being investigated as antifibrotic agents (e.g. WO2005113568, WO2005113569, WO2014067986, WO2016120403, US20140099319, WO2019067702, WO20190750 45, see WO2014078655, WO2020078807, WO2020078808 and WO2020210308 ).

본 발명은 갈렉틴-3 저해제인 신규한 식 (I) 의 화합물을 제공한다. 따라서, 본 화합물은 그것의 천연 탄수화물 리간드에 대한 Gal-3 결합의 조절이 지시되는 질환 및 장애의 예방 / 방지 또는 치료에 유용할 수 있다.The present invention provides novel compounds of formula (I) that are galectin-3 inhibitors. Accordingly, the present compound may be useful in the prevention/prevention or treatment of diseases and disorders directed at modulation of Gal-3 binding to its natural carbohydrate ligand.

1) 첫번째 실시형태에서, 본 발명은 식 (I) (식에서 절대 배치는 해당 식에 도시된 바와 같다고 이해된다) 의 화합물:1) In a first embodiment, the invention relates to compounds of formula (I) (wherein the absolute configuration is understood to be as shown in the formula):

식에서In Eq.

n 및 m 은 각각, 독립적으로, 정수 1 또는 2 를 나타내며, n+m 은 2 또는 3 이고; n and m each independently represent the integer 1 or 2, and n+m is 2 or 3;

X 는 O 또는 NR 2 를 나타내며; 여기에서 R 2 는 수소, C1-3-알킬 (특히 메틸 또는 에틸), -CO-H, -SO2-C1-3-알킬 (특히 SO2-CH3), 또는 -CO-C1-3-알킬 (특히 -CO-CH3) 을 나타내고; X represents O or N R 2 ; where R 2 is hydrogen, C 1-3 -alkyl (especially methyl or ethyl), -CO-H, -SO 2 -C 1-3 -alkyl (especially SO 2 -CH 3 ), or -CO-C 1-3 -alkyl (especially -CO-CH 3 );

Ar 1 은 하기를 나타내고 Ar 1 represents the following

· 아릴 (특히 페닐), 이는 일-, 이-, 삼-, 사-, 또는 오-치환 (특히 이-, 또는 삼-치환) 되며, 여기에서 치환기는 독립적으로 할로겐; 메틸; 시아노; 메톡시; 트리플루오로메틸; 트리플루오로메톡시; 및 NR N11 R N12 로부터 선택되며, 여기에서 R N11 은 수소를 나타내고 R N12 는 히드록시-C2-3-알킬을 나타내거나, 또는 R N11 및 R N12 는 그들이 부착되어 있는 질소 원자와 함께 모르폴린-4-일, 아제티딘-1-일, 피롤리딘-1-일, 및 피페리딘-1-일로부터 선택되는 4- 내지 6-원 헤테로시클릴을 형성하며, 상기 4- 내지 6-원 헤테로시클릴은 미치환 또는 히드록시로 일-치환됨 (특히 치환기는 독립적으로 할로겐, 또는 메틸로부터 선택됨);· Aryl (especially phenyl), which may be mono-, di-, tri-, tetra-, or penta-substituted (especially di-, or tri-substituted), wherein the substituents are independently halogen; methyl; cyano; methoxy; trifluoromethyl; trifluoromethoxy; and NR N11 R N12 , wherein R N11 represents hydrogen and R N12 represents hydroxy-C 2-3 -alkyl, or R N11 and R N12 together with the nitrogen atom to which they are attached are Forming a 4- to 6-membered heterocyclyl selected from polin-4-yl, azetidin-1-yl, pyrrolidin-1-yl, and piperidin-1-yl, wherein the 4- to 6-membered heterocyclyl is selected from - the original heterocyclyl is unsubstituted or mono-substituted with hydroxy (in particular the substituents are independently selected from halogen, or methyl);

· 5- 또는 6-원 헤테로아릴, 상기 5- 또는 6-원 헤테로아릴은 독립적으로 미치환, 일- 또는 이-치환되며, 여기에서 치환기는 독립적으로 할로겐, 메틸, 시아노, 및 메톡시로부터 선택됨; 또는· 5- or 6-membered heteroaryl, wherein the 5- or 6-membered heteroaryl is independently unsubstituted, mono- or di-substituted, wherein the substituents are independently selected from halogen, methyl, cyano, and methoxy. ; or

· 9- 또는 10-원 헤테로아릴, 상기 9- 또는 10-원 헤테로아릴은 독립적으로 미치환, 또는 메틸로 일-치환됨;· 9- or 10-membered heteroaryl, wherein the 9- or 10-membered heteroaryl is independently unsubstituted or mono-substituted with methyl;

R 1 은 하기를 나타내고 R 1 represents the following

· 히드록시; · hydroxy;

· C1-3-알콕시;· C 1-3 -alkoxy;

· -O-CO-C1-3-알킬; · -O-CO-C 1-3 -alkyl;

· -O-CH2-CH2-OH; 또는 · -O-CH 2 -CH 2 -OH; or

· -O-CH2-CO-R 1X , 여기에서 R 1X 는 하기를 나타냄-O-CH 2 -CO- R 1X , where R 1X represents

≫ -히드록시; ≫ -hydroxy;

≫ 모르폴린-4-일; 또는 ≫ Morpholine-4-day; or

≫ -NR N21 R N22 , 여기에서 R N21 및 R N22 는 그들이 부착되어 있는 질소 원자와 함께 아제티딘-1-일, 피롤리딘-1-일, 및 피페리딘-1-일로부터 선택되는 4- 내지 6-원 헤테로시클릴을 형성하며, 상기 4- 내지 6-원 헤테로시클릴은 히드록시로 일-치환됨;≫ -N R N21 R N22 , wherein R N21 and R N22 together with the nitrogen atom to which they are attached are selected from azetidin-1-yl, pyrrolidin-1-yl, and piperidin-1-yl. forming a 4- to 6-membered heterocyclyl, wherein the 4- to 6-membered heterocyclyl is mono-substituted with hydroxy;

[이러한 치환기 R 1 은 특히 C1-3-알콕시 (특히 메톡시) 를 나타냄][These substituents R 1 represents especially C 1-3 -alkoxy (especially methoxy)]

L 은 직접 결합, 메틸렌, 또는 에틸렌 (특히 직접 결합) 을 나타내고; 및 L represents a direct bond, methylene, or ethylene (especially a direct bond); and

Ar 2 는 하기를 나타냄 Ar 2 represents

· 페닐 또는 5- 또는 6-원 헤테로아릴 (특히 페닐), 상기 페닐 또는 5- 또는 6-원 헤테로아릴은 독립적으로 미치환, 또는 일-, 이- 또는 삼-치환 (특히 일-, 또는 이-치환) 되며; 여기에서 치환기는 독립적으로 C1-6-알킬 (특히 메틸), C3-6-시클로알킬, -CH2-C3-6-시클로알킬, C1-3-플루오로알킬, C1-3-플루오로알콕시, C1-3-알콕시 (특히 메톡시), 할로겐, 모르폴린-4-일, 아미노, 에티닐, 및 시아노로부터 선택됨 (특히 독립적으로 C1-6-알킬 (특히 메틸), C1-3-알콕시 (특히 메톡시), 할로겐, 및 시아노로부터 선택됨);· Phenyl or 5- or 6-membered heteroaryl (especially phenyl), said phenyl or 5- or 6-membered heteroaryl is independently unsubstituted, or mono-, di- or tri-substituted (especially mono-, or di-substituted) -substituted); Here, the substituents are independently C 1-6 -alkyl (especially methyl), C 3-6 -cycloalkyl, -CH 2 -C 3-6 -cycloalkyl, C 1-3 -fluoroalkyl, C 1-3 -fluoroalkoxy, C 1-3 -alkoxy (especially methoxy), halogen, morpholin-4-yl, amino, ethynyl, and cyano (especially independently C 1-6 -alkyl (especially methyl) , C 1-3 -alkoxy (especially methoxy), halogen, and cyano);

· 9-원 바이시클릭 헤테로아릴 또는 10-원 바이시클릭 헤테로아릴, 상기 9- 또는 10-원 바이시클릭 헤테로아릴은 독립적으로 미치환, 일- 또는 이-치환되며, 여기에서 치환기는 독립적으로 메틸, 메톡시, 및 할로겐으로부터 선택됨; 또는· 9-membered bicyclic heteroaryl or 10-membered bicyclic heteroaryl, wherein the 9- or 10-membered bicyclic heteroaryl is independently unsubstituted, mono- or di-substituted, wherein the substituents are independently selected from methyl, methoxy, and halogen; or

· 나프틸;· naphthyl;

또는 이의 약학적으로 허용가능한 염에 관한 것이다.Or it relates to a pharmaceutically acceptable salt thereof.

하위 실시형태에서, 상기 식 (I) 의 화합물, 또는, 준용되는, 하기 식 (II), (III) 또는 (IV) 의 화합물에서 헤테로시클로알칸을 분자의 나머지로 연결하는 질소 및 상기 헤테로시클로알칸의 히드록시 치환기는, 해당 식에 도시된 바와 같이, 상대적 트랜스 배치로 존재한다. 의심을 피하기 위해, 식 (I) 의 화합물은 특히 하기 실시형태 3) 에 나타낸 바와 같은 식 (IS) 의 화합물, 하기 실시형태 4) 에 나타낸 바와 같은 식 (IR) 의 화합물, 또는 이들의 임의의 혼합물이다.In a subembodiment, a nitrogen linking a heterocycloalkane to the remainder of the molecule in a compound of formula (I), or, mutatis mutandis, a compound of formula (II), (III) or (IV) below, and said heterocycloalkane The hydroxy substituents of exist in relative trans configuration, as shown in the formula. For the avoidance of doubt, the compound of formula (I) is in particular a compound of formula ( IS ) as shown in embodiment 3) below, a compound of formula ( IR ) as shown in embodiment 4) below, or a compound thereof It is a random mixture.

2) 본 발명의 두번째 양태는 실시형태 1) 에 따른 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 또한 식 (II), 식 (III) 또는 식 (IV) (식에서 절대 배치는 해당 식에 도시된 바와 같다고 이해된다) 의 화합물이다:2) A second aspect of the invention relates to compounds of formula (I) according to embodiment 1), which compounds may also be of formula (II), formula (III) or formula (IV) (wherein the absolute placement is in the corresponding formula) (understood as shown) is a compound of:

각각의 식 (II), 식 (III) 또는 식 (IV) 에서, 기 X, Ar 1 , Ar 2 , R 1 , 및 L 은 독립적으로 실시형태 1) 에서 정의된 바와 같다.In each formula (II), formula (III) or formula (IV), the groups X , Ar 1 , Ar 2 , R 1 , and L are independently as defined in embodiment 1).

첫번째 하위 실시형태에서, 실시형태 2) 의 화합물은 식 (II), (III), 또는 (IV) 의 화합물을 나타내며, 식에서 X 는 O 이고; 기 Ar 1 , Ar 2 , R 1 , 및 L 은 독립적으로 실시형태 1) 에서 정의된 바와 같다.In a first subembodiment, the compounds of embodiment 2) represent compounds of formula (II), (III), or (IV), wherein X is O; The groups Ar 1 , Ar 2 , R 1 , and L are independently as defined in embodiment 1).

두번째 하위 실시형태에서, 실시형태 2) 의 화합물은 식 (II), (III), 또는 (IV) 의 화합물을 나타내며, 식에서 X 는 NR 2 이고; 여기에서 R 2 는 수소, C1-3-알킬 (특히 메틸 또는 에틸), -CO-H, -SO2-C1-3-알킬 (특히 SO2-CH3), -CO-C1-3-알킬 (특히 -CO-CH3) 을 나타내고; 기 Ar 1 , Ar 2 , R 1 , 및 L 은 독립적으로 실시형태 1) 에서 정의된 바와 같다.In a second subembodiment, the compound of embodiment 2) represents a compound of formula (II ) , ( III), or (IV), wherein where R 2 is hydrogen, C 1-3 -alkyl (especially methyl or ethyl), -CO-H, -SO 2 -C 1-3 -alkyl (especially SO 2 -CH 3 ), -CO-C 1-3 -alkyl ( In particular -CO-CH 3 ); The groups Ar 1 , Ar 2 , R 1 , and L are independently as defined in embodiment 1).

3) 본 발명의 세번째 양태는 실시형태 1) 에 따른 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 또한 식 (IS) (식에서 절대 배치는 해당 식에 도시된 바와 같다고 이해된다) 의 화합물이다:3) A third aspect of the invention relates to compounds of formula (I) according to embodiment 1), which compounds are also compounds of formula ( IS ) (wherein the absolute configuration is understood to be as shown in the formula) am:

식에서 기 X, Ar 1 , Ar 2 , R 1 , L, m, 및 n 은 실시형태 1) 에서 정의된 바와 같다. 특정 실시형태에서, 상기 (IS) 의 화합물은 또한 식 (IIS), 식 (IIIS) 또는 식 (IVS) (식에서 절대 배치는 해당 식에 도시된 바와 같다고 이해된다) 의 화합물이다:In the formula, the groups X , Ar 1 , Ar 2 , R 1 , L , m , and n are as defined in embodiment 1). In certain embodiments, the compound of (IS ) is also a compound of formula (II S ), formula (III S ), or formula (IV S ) (wherein the absolute configuration is understood to be as shown in the formula):

각각의 식 (IIS), 식 (IIIS) 또는 식 (IVS) 에서, 기 X, Ar 1 , Ar 2 , R 1 , 및 L 은 독립적으로 실시형태 1) 에서 정의된 바와 같다.In each Formula (II S ), Formula (III S ) or Formula (IV S ), the groups X , Ar 1 , Ar 2 , R 1 , and L are independently as defined in embodiment 1).

첫번째 하위 실시형태에서, 실시형태 3) 의 화합물은 식 (IIS), (IIIS), 또는 (IVS) 의 화합물을 나타내며, 식에서 X 는 O 이고; Ar 1 , Ar 2 , R 1 , 및 L 은 독립적으로 실시형태 1) 에서 정의된 바와 같다.In a first subembodiment, the compounds of embodiment 3) represent compounds of the formula (II S ), (III S ), or (IV S ), wherein X is O; Ar 1 , Ar 2 , R 1 , and L are independently as defined in embodiment 1).

두번째 하위 실시형태에서, 실시형태 3) 의 화합물은 식 (IIS), (IIIS), 또는 (IVS) 의 화합물을 나타내며, 식에서 X 는 NR 2 이고; 여기에서 R 2 는 수소, C1-3-알킬 (특히 메틸 또는 에틸), -CO-H, -SO2-C1-3-알킬 (특히 SO2-CH3), -CO-C1-3-알킬 (특히 -CO-CH3) 을 나타내고; 기 Ar 1 , Ar 2 , R 1 , 및 L 은 독립적으로 실시형태 1) 에서 정의된 바와 같다.In a second subembodiment, the compounds of embodiment 3) represent compounds of the formula (II S ), ( III S ), or (IV S ), wherein where R 2 is hydrogen, C 1-3 -alkyl (especially methyl or ethyl), -CO-H, -SO 2 -C 1-3 -alkyl (especially SO 2 -CH 3 ), -CO-C 1-3 -alkyl ( In particular -CO-CH 3 ); The groups Ar 1 , Ar 2 , R 1 , and L are independently as defined in embodiment 1).

4) 본 발명의 또다른 양태는 실시형태 1) 에 따른 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 또한 식 (IR) (식에서 절대 배치는 해당 식에 도시된 바와 같다고 이해된다) 의 화합물이다: 4) Another aspect of the invention relates to compounds of formula (I) according to embodiment 1), which compounds also have the formula (I R ) (wherein the absolute configuration is understood to be as shown in the formula): It is a compound:

식에서 기 X, Ar 1 , Ar 2 , R 1 , L, m 및 n 은 독립적으로 실시형태 1) 에서 정의된 바와 같다. 특정 실시형태에서, 상기 식 (IR) 의 화합물은 또한 식 (IIR), 식 (IIIR) 또는 식 (IVR) (식에서 절대 배치는 해당 식에 도시된 바와 같다고 이해된다) 의 화합물이다:In the formula, the groups X , Ar 1 , Ar 2 , R 1 , L , m and n are independently as defined in embodiment 1). In certain embodiments, the compound of formula (I R ) is also a compound of formula (I R ), formula (III R ), or formula (I R ) (wherein the absolute configuration is understood to be as shown in the formula) :

각각의 식 (IIR), 식 (IIIR) 또는 식 (IVR) 에서, 기 X, Ar 1 , Ar 2 , R 1 , 및 L 은 독립적으로 실시형태 1) 에서 정의된 바와 같다.In each Formula (I R ), Formula (III R ) or Formula (I R ), the groups X , Ar 1 , Ar 2 , R 1 , and L are independently as defined in embodiment 1).

첫번째 하위 실시형태에서, 실시형태 4) 의 화합물은 식 (IIR), (IIIR), 또는 (IVR) 의 화합물을 나타내며, 식에서 X 는 O 이고; 기 Ar 1 , Ar 2 , R 1 , 및 L 은 독립적으로 실시형태 1) 에서 정의된 바와 같다.In a first subembodiment, the compounds of embodiment 4) represent compounds of the formula (I R ), (III R ), or (I R ), wherein X is O; The groups Ar 1 , Ar 2 , R 1 , and L are independently as defined in embodiment 1).

두번째 하위 실시형태에서, 실시형태 4) 의 화합물은 식 (IIR), (IIIR), 또는 (IVR) 의 화합물을 나타내며, 식에서 X 는 NR 2 이고; 여기에서 R 2 는 수소, C1-3-알킬 (특히 메틸 또는 에틸), -CO-H, -SO2-C1-3-알킬 (특히 SO2-CH3), -CO-C1-3-알킬 (특히 -CO-CH3) 을 나타내고; 기 Ar 1 , Ar 2 , R 1 , 및 L 은 독립적으로 실시형태 1) 에서 정의된 바와 같다.In a second subembodiment, the compounds of embodiment 4) represent compounds of the formula (I R ), (III R ), or (I R ), wherein X is NR 2 ; where R 2 is hydrogen, C 1-3 -alkyl (especially methyl or ethyl), -CO-H, -SO 2 -C 1-3 -alkyl (especially SO 2 -CH 3 ), -CO-C 1-3 -alkyl ( In particular -CO-CH 3 ); The groups Ar 1 , Ar 2 , R 1 , and L are independently as defined in embodiment 1).

식 (I) 의 화합물은 테트라히드로피란 모이어티에 위치하고 식 (I) 에 관해 도시된 절대 배치로 존재하는 5 개의 입체 또는 비대칭 중심을 함유한다. 식 (I) 의 화합물은 헤테로시클로알칸 모이어티에 위치하는 2 개의 입체 또는 비대칭 중심을 추가로 함유한다. 특정 실시형태에서, 상기 식 (I) 의 화합물, 또는, 준용하여, 식 (II), (III) 또는 (IV) 의 화합물에서 헤테로시클로알칸을 분자의 나머지로 연결하는 질소 및 상기 헤테로시클로알칸의 히드록시 치환기는, 해당 식에 도시된 바와 같이, 상대적 트랜스 배치로 존재한다. 의심을 피하기 위해, 식 (I) 의 화합물은 특히 실시형태 3) 에 나타낸 바와 같은 식 (IS) 의 화합물, 실시형태 4) 에 나타낸 바와 같은 식 (IR) 의 화합물, 또는 이들의 임의의 혼합물이다.Compounds of formula (I) contain five steric or asymmetric centers located on the tetrahydropyran moiety and present in the absolute configuration shown with respect to formula (I). Compounds of formula (I) additionally contain two steric or asymmetric centers located in the heterocycloalkane moiety. In certain embodiments, in a compound of formula (I), or, mutatis mutandis, a compound of formula (II), (III) or (IV), the nitrogen linking the heterocycloalkane to the remainder of the molecule and the heterocycloalkane Hydroxy substituents exist in relative trans configuration, as shown in the formula. For the avoidance of doubt, the compound of formula (I) is in particular a compound of formula ( IS ) as shown in embodiment 3), a compound of formula ( IR ) as shown in embodiment 4), or any of these. It is a mixture.

또한, 식 (I) 의 화합물은 하나, 및 가능하게는 그 이상의 입체 또는 비대칭 중심, 예컨대 하나 이상의 추가의 비대칭 탄소 원자를 함유할 수 있다. 따라서, 식 (I) 의 화합물은 입체이성질체의 혼합물로서 또는 바람직하게는 순수한 입체이성질체로서 존재할 수 있다. 입체이성질체의 혼합물은 당업자에 공지된 방식으로 분리될 수 있다.Additionally, the compounds of formula (I) may contain one and possibly more steric or asymmetric centers, such as one or more additional asymmetric carbon atoms. Accordingly, the compounds of formula (I) may exist as mixtures of stereoisomers or, preferably, as pure stereoisomers. Mixtures of stereoisomers can be separated in a manner known to those skilled in the art.

특정한 화합물 (또는 일반적인 구조) 이 특정한 절대 배치, 예를 들어 (R)- 또는 (S)-거울상이성질체로서 지정되는 경우, 이러한 지정은 풍부한, 특히 본질적으로 순수한, 거울상이성질체 형태의 각각의 화합물 (또는 일반적인 구조) 을 나타내는 것으로 이해해야 한다. 마찬가지로, 화합물에서의 특정한 비대칭 중심이 (R)- 또는 (S)-배치인 것으로서 또는 특정한 상대적 배치인 것으로서 지정되는 경우, 이러한 지정은 상기 비대칭 중심의 각각의 배치에 대해 풍부한, 특히 본질적으로 순수한 형태인 화합물을 나타내는 것으로 이해해야 한다. 유사하게, 예를 들어 시클릭 기에서의 2 개의 입체 중심은 특정한 상대적인 배치로 존재할 수 있다.When a particular compound (or general structure) is designated as a specific absolute configuration, for example (R)- or (S)-enantiomer, this designation refers to the respective compound in its abundant, especially essentially pure, enantiomeric form (or It should be understood as representing a general structure. Likewise, when a particular asymmetric center in a compound is designated as being in the (R)- or (S)-configuration or as being in a particular relative configuration, this designation refers to the abundance, especially in essentially pure form, of each configuration of said asymmetric center. It should be understood as representing a phosphorus compound. Similarly, the two stereogenic centers, for example in a cyclic group, may exist in a particular relative configuration.

용어 "풍부한" 은, 입체이성질체의 맥락에서 사용되는 경우, 본 발명의 맥락에서, 각각의 입체이성질체가 각각의 다른 입체이성질체 / 각각의 다른 입체이성질체의 전체에 대해서, 적어도 70:30, 특히 적어도 90:10 의 비로 (즉, 적어도 70 중량%, 특히 적어도 90 중량% 의 순도로) 존재한다는 것을 의미하는 것으로 이해해야 한다.The term "enriched", when used in the context of stereoisomers, means, in the context of the present invention, that each stereoisomer is present in a ratio of at least 70:30 to the respective other stereoisomer/total of each other stereoisomer, in particular at least 90 :10 (i.e. in a purity of at least 70% by weight, especially at least 90% by weight).

용어 "본질적으로 순수한" 은, 입체이성질체의 맥락에서 사용되는 경우, 본 발명의 맥락에서, 각각의 입체이성질체가 각각의 다른 입체이성질체 / 각각의 다른 입체이성질체의 전체에 대해서, 적어도 95 중량%, 특히 적어도 99 중량% 의 순도로 존재한다는 것을 의미하는 것으로 이해해야 한다.The term "essentially pure", when used in the context of stereoisomers, in the context of the present invention means that each stereoisomer is present in at least 95% by weight, relative to the total of each other stereoisomer/each other stereoisomer, in particular It should be understood to mean present in a purity of at least 99% by weight.

본 발명은 또한 동위원소 표지된, 특히 2H (중수소) 표지된 구현예 1) 내지 18) 에 따른 식 (I) 의 화합물을 포함하고, 이 화합물은 하나 이상의 원자가 동일한 원자 번호를 갖지만 천연에서 일반적으로 발견되는 원자 질량과 상이한 원자 질량을 갖는 원자로 각각 대체된다는 것을 제외하고는 식 (I) 의 화합물과 동일하다. 동위원소 표지된, 특히 2H (중수소) 표지된 식 (I), (II), (III), (IV), (IS), (IIS), (IIIS), (IVS), (IR), (IIR), (IIIR), (IVR) 및 (V) 의 화합물 및 이의 염은 본 발명의 범주 내에 있다. 수소를 보다 무거운 동위 원소 2H (중수소) 로 치환하면, 더 큰 대사 안정성, 따라서 예를 들어 생체내 반감기의 증가 또는 투약량 요건의 감소를 유도할 수 있거나, 사이토크롬 P450 효소 저해의 감소, 따라서 예를 들어 안전성 프로파일의 개선을 유도할 수 있다. 본 발명의 한 구현예에서, 식 (I) 의 화합물은 동위원소 표지되지 않거나, 이들은 하나 이상의 중수소 원자로만 표지된다. 하위 구현예에서, 식 (I) 의 화합물은 전혀 동위원소 표지되지 않는다. 식 (I) 의 동위원소 표지된 화합물은 이하 기재된 방법과 유사하게, 그러나 적합한 시약 또는 출발 물질의 적절한 동위원소 변화를 사용하여 제조할 수 있다.The invention also includes compounds of formula (I) according to embodiments 1) to 18) that are isotopically labeled, in particular 2 H (deuterium) labeled, wherein one or more atoms have the same atomic number but are common in nature. Identical to the compounds of formula (I) except that each is replaced by an atom with an atomic mass different from the atomic mass found with . Isotopically labeled, especially 2 H (deuterium) labeled formula (I), (II), (III), (IV), (I S ), (II S ), (III S ), (IV S ), Compounds of (I R ), (I R ), (III R ), (I R ) and (V) and salts thereof are within the scope of the present invention. Substitution of hydrogen with the heavier isotope 2H (deuterium) can lead to greater metabolic stability, thus for example increased half-life in vivo or reduced dosage requirements, or decreased cytochrome P450 enzyme inhibition, thus e.g. For example, it can lead to an improvement in the safety profile. In one embodiment of the invention, the compounds of formula (I) are not isotopically labeled, or they are labeled only with one or more deuterium atoms. In a subembodiment, the compounds of formula (I) are not isotopically labeled at all. Isotopically labeled compounds of formula (I) can be prepared analogously to the methods described below, but using suitable reagents or appropriate isotopic changes in the starting materials.

본 특허 출원에서, 점선으로서 도시된 결합은 도시된 라디칼의 부착점을 나타낸다. 예를 들어, 하기 도시된 라디칼: In this patent application, bonds shown as dashed lines represent the points of attachment of the radicals shown. For example, the radical shown below:

은 3-플루오로페닐 기이다.is a 3-fluorophenyl group.

화합물, 염, 약학적 조성물, 질환 등에 대해 복수 형태가 사용되는 경우, 이는 또한 단일 화합물, 염 등을 의미하는 것으로 의도된다.When the plural form is used for compounds, salts, pharmaceutical compositions, diseases, etc., it is also intended to mean a single compound, salt, etc.

구현예 1) 내지 18) 에 따른 식 (I) 의 화합물에 대한 임의의 언급은, 적절하고 편리한 경우에, 이러한 화합물의 염 (및 특히 약학적으로 허용가능한 염) 을 또한 언급하는 것으로 이해해야 한다. Any reference to compounds of formula (I) according to embodiments 1) to 18) should, where appropriate and convenient, also be understood as referring to salts (and especially pharmaceutically acceptable salts) of these compounds.

용어 "약학적으로 허용가능한 염" 은, 대상 화합물의 원하는 생물학적 활성을 보유하며 최소한의 원치 않는 독성학적 효과를 나타내는 염을 나타낸다. 이러한 염은, 대상 화합물에서의 염기성 및/또는 산성 기의 존재에 따라, 무기 또는 유기 산 및/또는 염기 부가 염을 포함한다. 참고로, 예를 들어 "Handbook of Pharmaceutical Salts. Properties, Selection and Use.", P. Heinrich Stahl, Camille G. Wermuth (Eds.), Wiley-VCH, 2008; 및 "Pharmaceutical Salts and Co-crystals", Johan Wouters and Luc Quere (Eds.), RSC Publishing, 2012 를 참조한다.The term “pharmaceutically acceptable salt” refers to a salt that retains the desired biological activity of the compound of interest and exhibits minimal unwanted toxicological effects. These salts include inorganic or organic acid and/or base addition salts, depending on the presence of basic and/or acidic groups in the compound of interest. For reference, see, for example, "Handbook of Pharmaceutical Salts. Properties, Selection and Use.", P. Heinrich Stahl, Camille G. Wermuth (Eds.), Wiley-VCH, 2008; and “Pharmaceutical Salts and Co-crystals”, Johan Wouters and Luc Quere (Eds.), RSC Publishing, 2012.

본원에서 제공되는 정의는, 구현예 1) 내지 17) 중 어느 하나에서 정의하는 바와 같은 식 (I), (II), (III), (IV), (IS), (IIS), (IIIS), (IVS), (IR), (IIR), (IIIR), (IVR) 및 (V) 의 화합물에 균일하게 적용되며, 달리 명시적으로 제시된 정의가 보다 넓거나 보다 좁은 정의를 제공하지 않는 한, 발명의 설명 및 청구범위 전체에 걸쳐서 준용되는 것으로 의도된다. 용어의 정의 또는 바람직한 정의가 본원에서 정의된 바와 같은 임의의 또는 모든 다른 용어의 임의의 정의 또는 바람직한 정의와 관계없이 (그리고 이와 조합으로) 각각의 용어를 규정하고 대체할 수 있다는 것이 잘 이해된다.The definitions provided herein refer to Formulas (I), (II), (III), (IV), ( IS ), (II S ), ( Applies uniformly to the compounds III S ), (IV S ), (I R ), (I R ), (III R ), (I R ) and (V), unless otherwise explicitly given definitions are broader or Unless a narrower definition is provided, this is intended to apply mutatis mutandis throughout the description and claims. It is well understood that a definition or preferred definition of a term may specify and replace each term without regard to (and in combination with) any definition or preferred definition of any or all other terms as defined herein.

본 특허 출원에서, 화합물은 IUPAC 명명법을 사용하여 지명되지만, 탄수화물 명명법을 사용해서도 지명될 수 있다. 따라서, 모이어티:In this patent application, compounds are named using IUPAC nomenclature, but may also be named using carbohydrate nomenclature. Therefore, the moiety:

는 (2R,3R,4S,5R,6R)-3,5-디히드록시-6-(히드록시메틸)-4-(4-페닐-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르보닐 또는, 대안적으로, 1,3-디-데옥시-3-[4-페닐-1H-1,2,3-트리아졸-1-일]-β-D-갈락토피라노시드-1-카르보닐로 명명될 수 있으며, 분자의 나머지에 대한 부착점인 카르보닐 기를 가지는 탄소 원자의 절대 배치는 각각 (2R)-, 베타-배치이다. 예를 들어, 화합물 (2R,3R,4S,5R,6R)-N-(3-클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드는 또한 1,3-디-데옥시-2-O-메틸-3-[4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일]-N-(3-클로로페닐)-N-((3S,4R)-4-히드록시-3-테트라히드로푸라닐)-베타-D-갈락토-피라노스-1-카르복사미드를 지칭하는 것으로 이해된다.is (2R,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-phenyl-1H-1,2,3-triazol-1-yl ) tetrahydro-2H-pyran-2-carbonyl or, alternatively, 1,3-di-deoxy-3-[4-phenyl-1H-1,2,3-triazol-1-yl]- It can be named β-D-galactopyranoside-1-carbonyl, and the absolute configuration of the carbon atom with the carbonyl group as the point of attachment to the rest of the molecule is (2R)-, beta-configuration, respectively. For example, the compound (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4- Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra Hydro-2H-pyran-2-carboxamide is also known as 1,3-di-deoxy-2-O-methyl-3-[4-(3,4,5-trifluorophenyl)-1H-1, 2,3-triazol-1-yl]-N-(3-chlorophenyl)-N-((3S,4R)-4-hydroxy-3-tetrahydrofuranyl)-beta-D-galacto- It is understood to refer to pyranose-1-carboxamide.

치환기가 임의적인 것으로서 표시될 때마다, 이러한 치환기는 부재할 수 있으며 (즉, 각각의 잔기는 그러한 임의적 치환기에 관하여 미치환된다), 이 경우, 유리 원자가를 갖는 모든 위치 (이러한 임의적인 치환기가 부착될 수 있는 곳; 예를 들어 방향족 고리에서, 고리 탄소 원자 및/또는 유리 원자가를 갖는 고리 질소 원자) 는, 적절한 경우 수소로 치환되는 것으로 이해된다. 마찬가지로, 용어 "선택적으로" 가 (고리) 헤테로원자(들)의 맥락에서 사용되는 경우, 이 용어는, 각각의 임의적인 헤테로원자(들) 등이 부재하거나 (즉, 특정한 모이어티는 헤테로원자(들) 를 함유하지 않으며 / 카르보사이클 / 등이다), 각각의 임의적인 헤테로원자(들) 등이 명시적으로 정의한 바와 같이 존재한다는 것을 의미한다. 각각의 구현예 또는 청구범위에서 달리 명시적으로 정의하지 않는 한, 본원에서 정의하는 기는 미치환된다.Whenever a substituent is indicated as optional, such substituent may be absent (i.e., each residue is unsubstituted with respect to such optional substituent), in which case all positions having a free valency (such optional substituent may be attached It is understood that where appropriate; for example in aromatic rings, ring carbon atoms and/or ring nitrogen atoms with free valency), where appropriate, they are substituted by hydrogen. Likewise, when the term "optionally" is used in the context of (ring) heteroatom(s), the term means that each optional heteroatom(s), etc. is absent (i.e., the particular moiety is a heteroatom ( / carbocycle / etc.), and each optional heteroatom(s) etc. is present as explicitly defined. Unless explicitly defined otherwise in each embodiment or claim, the groups defined herein are unsubstituted.

용어 "할로겐" 은 불소, 염소, 브롬 또는 요오드 (특히 불소, 염소 또는 브롬) 를 의미한다.The term “halogen” means fluorine, chlorine, bromine or iodine (especially fluorine, chlorine or bromine).

단독으로 또는 조합으로 사용되는 용어 "알킬" 은, 1 내지 6 개의 탄소 원자를 함유하는 포화 직쇄 또는 분지쇄 탄화수소기를 지칭한다. 용어 "Cx-y-알킬" (x 및 y 각각은 정수임) 은 x 내지 y 개의 탄소 원자를 함유하는 상기에서 정의된 바와 같은 알킬 기를 지칭한다. 예를 들어, C1-6-알킬 기는 1 내지 6 개의 탄소 원자를 함유한다. 알킬 기의 대표예는 메틸, 에틸, 프로필, 이소프로필, 부틸, 이소부틸, tert.-부틸, 펜틸, 3-메틸-부틸, 2,2-디메틸-프로필 및 3,3-디메틸-부틸이다. 메틸이 바람직하다. 의심의 여지를 피하기 위해, 기가 예를 들어 프로필 또는 부틸로서 지칭되는 경우, 이것은 각각 n-프로필, n-부틸인 것을 의미한다. Ar 1 또는 Ar 2 의 치환기가 "C1-6-알킬" 을 나타내는 경우에, 이 용어는 특히 메틸을 지칭한다. R 2 가 "C1-6-알킬" 을 나타내는 경우에, 이 용어는 특히 메틸 또는 에틸을 지칭한다. 용어 "C1-3-알킬" 이 R 2 의 치환기에 대해 사용되는 경우에, 예컨대 "-SO2-C1-3-알킬" 또는 "-CO-C1-3-알킬" 에서, 이 용어는 특히 메틸을 지칭한다.The term “alkyl,” used alone or in combination, refers to a saturated straight-chain or branched-chain hydrocarbon group containing 1 to 6 carbon atoms. The term “C xy -alkyl” (where x and y are each an integer) refers to an alkyl group as defined above containing x to y carbon atoms. For example, a C 1-6 -alkyl group contains 1 to 6 carbon atoms. Representative examples of alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert.-butyl, pentyl, 3-methyl-butyl, 2,2-dimethyl-propyl and 3,3-dimethyl-butyl. Methyl is preferred. For the avoidance of doubt, if a group is referred to for example as propyl or butyl, this means n-propyl, n-butyl respectively. In case the substituent on Ar 1 or Ar 2 represents “C 1-6 -alkyl” this term refers in particular to methyl. In case R 2 represents “C 1-6 -alkyl” this term refers in particular to methyl or ethyl. When the term "C 1-3 -alkyl" is used for a substituent of R 2 , for example in "-SO 2 -C 1-3 -alkyl" or "-CO-C 1-3 -alkyl", the term refers particularly to methyl.

단독으로 또는 조합으로 사용되는 용어 "플루오로알킬" 은 하나 이상의 (및 가능하게는 모든) 수소 원자가 불소로 대체된, 1 내지 3 개의 탄소 원자를 함유하는, 상기에서 정의한 바와 같은 알킬 기를 지칭한다. 용어 "Cx-y-플루오로알킬" (x 및 y 각각은 정수임) 은 x 내지 y 개의 탄소 원자를 함유하는 상기에서 정의된 바와 같은 플루오로알킬 기를 지칭한다. 예를 들어, C1-3-플루오로알킬 기는 1 내지 7 개의 수소 원자가 불소로 대체된, 1 내지 3 개의 탄소 원자를 함유한다. The term “fluoroalkyl”, used alone or in combination, refers to an alkyl group as defined above containing 1 to 3 carbon atoms in which one or more (and possibly all) hydrogen atoms have been replaced by fluorine. The term “C xy -fluoroalkyl” (where x and y are each an integer) refers to a fluoroalkyl group as defined above containing x to y carbon atoms. For example, a C 1-3 -fluoroalkyl group contains 1 to 3 carbon atoms with 1 to 7 hydrogen atoms replaced by fluorine.

단독으로 또는 조합으로 사용되는 용어 "플루오로알콕시" 는 하나 이상의 (및 가능하게는 모든) 수소 원자가 불소로 대체된, 1 내지 3 개의 탄소 원자를 함유하는, 상기에서 정의한 바와 같은 알콕시 기를 지칭한다. 용어 "Cx-y-플루오로알콕시" (x 및 y 각각은 정수임) 는 x 내지 y 개의 탄소 원자를 함유하는 상기에서 정의된 바와 같은 플루오로알콕시 기를 지칭한다. 예를 들어, C1-3-플루오로알콕시 기는 1 내지 7 개의 수소 원자가 불소로 대체된, 1 내지 3 개의 탄소 원자를 함유한다.The term “fluoroalkoxy”, used alone or in combination, refers to an alkoxy group as defined above, containing 1 to 3 carbon atoms, in which one or more (and possibly all) hydrogen atoms have been replaced by fluorine. The term “C xy -fluoroalkoxy” (x and y each being an integer) refers to a fluoroalkoxy group as defined above containing x to y carbon atoms. For example, a C 1-3 -fluoroalkoxy group contains 1 to 3 carbon atoms, with 1 to 7 hydrogen atoms replaced by fluorine.

단독으로 또는 조합으로 사용된 용어 "시클로알킬" 은 특히 포화 모노시클릭, 또는 3 내지 8 개의 탄소 원자를 함유하는 융합된-, 가교된-, 또는 스피로-바이시클릭 탄화수소 고리를 지칭한다. 용어 "Cx-y-시클로알킬" (x 및 y 각각은 정수임) 은 x 내지 y 개의 탄소 원자를 함유하는 상기에서 정의된 바와 같은 시클로알킬 기를 지칭한다. 예를 들어, C3-6-시클로알킬 기는 3 내지 6 개의 탄소 원자를 함유한다. 시클로알킬 기의 예는 시클로프로필, 시클로부틸, 시클로펜틸 및 시클로헥실이다.The term “cycloalkyl,” used alone or in combination, refers particularly to a saturated monocyclic, or fused-, bridged-, or spiro-bicyclic hydrocarbon ring containing 3 to 8 carbon atoms. The term “C xy -cycloalkyl” (where x and y are each an integer) refers to a cycloalkyl group as defined above containing x to y carbon atoms. For example, a C 3-6 -cycloalkyl group contains 3 to 6 carbon atoms. Examples of cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

단독으로 또는 조합으로 사용되는 용어 "알콕시" 는 알킬 기가 상기에서 정의한 바와 같은 것인 알킬-O- 기를 지칭한다. 용어 "Cx-y-알콕시" (x 및 y 각각은 정수임) 는 x 내지 y 개의 탄소 원자를 함유하는 상기에서 정의한 바와 같은 알콕시 기를 지칭한다. 에톡시 및 특히 메톡시가 바람직하다. R 1 이 "C1-3-알콕시" 를 나타내는 경우, 용어는 특히 메톡시를 지칭한다. Ar 2 의 치환기가 "C1-3-알콕시" 를 나타내는 경우, 용어는 특히 메톡시를 지칭한다.The term “alkoxy” used alone or in combination refers to an alkyl-O- group wherein the alkyl group is as defined above. The term “C xy -alkoxy” (x and y each being an integer) refers to an alkoxy group as defined above containing x to y carbon atoms. Ethoxy and especially methoxy are preferred. R 1 When indicating “C 1-3 -alkoxy” the term refers in particular to methoxy. In case the substituent on Ar 2 represents “C 1-3 -alkoxy” the term refers in particular to methoxy.

단독 또는 조합으로 사용되는 용어 "아릴" 은 페닐 또는 나프틸, 특히 페닐을 의미하며, 여기서 상기 아릴 기는 미치환되거나 명시적으로 정의한 바와 같이 치환된다. 치환기 Ar 1 또는 Ar 2 가 "아릴" 을 나타내는 경우에, 이 용어는 특히 페닐을 의미한다.The term "aryl", used alone or in combination, means phenyl or naphthyl, especially phenyl, wherein the aryl group is unsubstituted or substituted as explicitly defined. In case the substituent Ar 1 or Ar 2 represents “aryl”, this term refers in particular to phenyl.

단독 또는 조합으로 사용되는, 그리고 더 넓거나 더 좁은 방식으로 명시적으로 정의되지 않는 경우 용어 "헤테로아릴" 은, 각각 산소, 질소 및 황에서 독립적으로 선택되는 1 개 내지 최대 4 개의 헤테로원자를 함유하는 5- 내지 10-원 모노시클릭 또는 바이시클릭 방향족 고리를 의미한다. 이러한 헤테로아릴 기의 대표예는 5-원 헤테로아릴 기, 예컨대 푸라닐, 옥사졸릴, 이속사졸릴, 옥사디아졸릴, 티오페닐, 티아졸릴, 이소티아졸릴, 티아디아졸릴, 피롤릴, 이미다졸릴, 피라졸릴, 트리아졸릴, 테트라졸릴; 6-원 헤테로아릴 기, 예컨대 피리디닐, 피리미디닐, 피리다지닐, 피라지닐; 및 8- 내지 10-원 바이시클릭 헤테로아릴 기, 예컨대 인돌릴, 이소인돌릴, 벤조푸라닐, 이소벤조푸라닐, 벤조티오페닐, 인다졸릴, 벤즈이미다졸릴, 벤족사졸릴, 벤즈이속사졸릴, 벤조티아졸릴, 벤조이소티아졸릴, 벤조트리아졸릴, 벤족사디아졸릴, 벤조티아디아졸릴, 티에노피리디닐, 퀴놀리닐, 이소퀴놀리닐, 나프티리디닐, 신놀리닐, 퀴나졸리닐, 퀴녹살리닐, 프탈라지닐, 피롤로피리디닐, 피라졸로피리디닐, 피라졸로피리미디닐, 피롤로피라지닐, 이미다조피리디닐, 이미다조피리다지닐 및 이미다조티아졸릴이다. 상기에서 언급한 헤테로아릴 기는 미치환되거나 명시적으로 정의한 바와 같이 치환된다.The term "heteroaryl", used alone or in combination, and unless explicitly defined in a broader or narrower manner, refers to a group of heteroatoms containing from 1 to up to 4 heteroatoms each independently selected from oxygen, nitrogen and sulfur. refers to a 5- to 10-membered monocyclic or bicyclic aromatic ring. Representative examples of such heteroaryl groups are 5-membered heteroaryl groups such as furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thiophenyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl. , pyrazolyl, triazolyl, tetrazolyl; 6-membered heteroaryl groups such as pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl; and 8- to 10-membered bicyclic heteroaryl groups such as indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl. , benzothiazolyl, benzoisothiazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, thienopyridinyl, quinolinyl, isoquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, They are quinoxalinyl, phthalazinyl, pyrrolopyridinyl, pyrazolopyridinyl, pyrazolopyrimidinyl, pyrrolopyrazinyl, imidazopyridinyl, imidazopyridazinyl and imidazothiazolyl. The heteroaryl groups mentioned above are unsubstituted or substituted as explicitly defined.

치환기 Ar 1 이 "5- 또는 6-원 헤테로아릴" 을 나타내는 경우에, 이 용어는 특히 티아졸릴 (특히 4-클로로티아졸-2-일) 을 의미한다. 치환기 Ar 2 가 "5- 또는 6-원 헤테로아릴" 을 나타내는 경우에, 이 용어는 특히 푸라닐, 티오페닐, 피롤릴, 티아졸릴, 이소티아졸릴, 이속사졸릴, 피라졸릴, 이미다졸릴, 피리디닐 또는 피리미디닐을 의미하고; 여기서 상기 5- 또는 6-원 헤테로아릴은 미치환되거나 명시적으로 정의된 바와 같이 치환된다.In case the substituent Ar 1 represents “5- or 6-membered heteroaryl”, this term means in particular thiazolyl (in particular 4-chlorothiazol-2-yl). In case the substituent Ar 2 represents “5- or 6-membered heteroaryl”, this term refers in particular to furanyl, thiophenyl, pyrrolyl, thiazolyl, isothiazolyl, isoxazolyl, pyrazolyl, imidazolyl, means pyridinyl or pyrimidinyl; wherein the 5- or 6-membered heteroaryl is unsubstituted or substituted as explicitly defined.

치환기 Ar 1 이 "9- 또는 10-원 바이시클릭 헤테로아릴" 을 나타내는 경우에, 이 용어는 특히 벤조티아졸릴 (특히 2-메틸벤조[d]티아졸-6-일) 을 의미한다. 치환기 Ar 2 가 "9-원 바이시클릭 헤테로아릴" 을 나타내는 경우에, 이 용어는 특히 인돌릴, 벤조티오페닐, 벤조티아졸릴, 또는 벤조이미다졸릴을 의미한다; 상기 9-원 바이시클릭 헤테로아릴은 미치환되거나 명시적으로 정의된 바와 같이 치환된다. 치환기 Ar 2 가 "10-원 바이시클릭 헤테로아릴" 을 나타내는 경우에, 이 용어는 특히 퀴놀리닐 또는 퀴녹살리닐을 의미한다; 상기 10-원 바이시클릭 헤테로아릴은 미치환되거나 명시적으로 정의된 바와 같이 치환된다.In case the substituent Ar 1 represents “9- or 10-membered bicyclic heteroaryl”, this term means in particular benzothiazolyl (in particular 2-methylbenzo[d]thiazol-6-yl). In case the substituent Ar 2 represents “9-membered bicyclic heteroaryl”, this term means in particular indolyl, benzothiophenyl, benzothiazolyl, or benzoimidazolyl; The 9-membered bicyclic heteroaryl is unsubstituted or substituted as explicitly defined. In case the substituent Ar 2 represents “10-membered bicyclic heteroaryl”, this term means in particular quinolinyl or quinoxalinyl; The 10-membered bicyclic heteroaryl is unsubstituted or substituted as explicitly defined.

용어 "시아노" 는 기 -CN 을 지칭한다.The term “cyano” refers to the group -CN.

단어 "사이" 를 사용하여 수치 범위를 설명할 때마다, 이것은 표시된 범위의 경계점이 명백히 범위 내에 포함되는 것으로 이해해야 한다. 예를 들어: 온도 범위가 40℃ 와 80℃ 사이인 것으로 기재되는 경우, 이것은 종말점 40℃ 및 80℃ 가 범위 내에 포함되는 것을 의미하거나; 변수가 1 과 4 사이의 정수인 것으로 정의되는 경우, 이것은 변수가 정수 1, 2, 3 또는 4 인 것을 의미한다. Whenever the word “between” is used to describe a numerical range, this should be understood to mean that the boundary points of the indicated range are expressly included within the range. For example: If a temperature range is described as being between 40°C and 80°C, this means that the endpoints 40°C and 80°C are included within the range; If a variable is defined as being an integer between 1 and 4, this means that the variable is the integer 1, 2, 3, or 4.

온도와 관련하여 사용되지 않는 한, 본 출원에서 수치 값 "X" 앞에 위치한 용어 "약" 은 X - X 의 10% 내지 X + X 의 10% 로 확장되는 간격, 바람직하게는 X - X 의 5% 내지 X + X 의 5% 로 확장되는 간격을 나타낸다. 온도의 특별한 경우에, 본 출원에서 온도 "Y" 앞에 위치한 용어 "약" 은 온도 Y - 10℃ 내지 Y + 10℃ 로 확장되는 간격, 바람직하게는 Y - 5℃ 내지 Y + 5℃ 로 확장되는 간격을 나타낸다. 또한, 본원에서 사용되는 용어 "실온" 은 약 25℃ 의 온도를 나타낸다.Unless used in relation to temperature, in this application the term "about" preceding a numerical value "X" means an interval extending from 10% of X - X to 10% of X + It represents an interval extending from % to 5% of X + X. In the special case of temperature, in the present application the term "about" preceding the temperature "Y" refers to the interval extending from the temperature Y - 10°C to Y + 10°C, preferably from Y - 5°C to Y + 5°C. Indicates the interval. Additionally, the term “room temperature” as used herein refers to a temperature of about 25°C.

본 발명의 추가의 실시형태가 이후 제시된다:Further embodiments of the invention are presented below:

5) 또다른 실시형태는 실시형태 1) 내지 4) 중 어느 하나에 따른 화합물에 관한 것으로, Ar 1 은 페닐을 나타내며, 이는 일-, 이-, 삼-, 사-, 또는 오-치환 (특히 이-, 또는 삼-치환) 되며, 여기에서 치환기는 독립적으로 할로겐; 메틸; 시아노; 및 메톡시로부터 선택된다.5) Another embodiment relates to a compound according to any one of embodiments 1) to 4), wherein Ar 1 represents phenyl, which is mono-, di-, tri-, tetra-, or penta-substituted (especially di-, or tri-substituted), wherein the substituents are independently halogen; methyl; cyano; and methoxy.

6) 또다른 실시형태는 실시형태 1) 내지 4) 중 어느 하나에 따른 화합물에 관한 것으로, Ar 1 은 페닐을 나타내며, 이는 이- 또는 삼-치환되며, 여기에서 치환기는 독립적으로 할로겐 및 메틸로부터 선택된다.6) Another embodiment relates to a compound according to any one of embodiments 1) to 4), wherein Ar 1 represents phenyl, which is di- or tri-substituted, wherein the substituents are independently selected from halogen and methyl.

하위 실시형태에서, 상기 치환기 중 적어도 하나는 상기 페닐의 메타- 또는 파라-위치에 부착되어 있다.In a subembodiment, at least one of the substituents is attached to the meta- or para- position of the phenyl.

7) 또다른 실시형태는 실시형태 1) 내지 4) 중 어느 하나에 따른 화합물에 관한 것으로, Ar 1 은 페닐을 나타내며, 이는 이- 또는 삼-치환되며, 7) Another embodiment relates to a compound according to any one of embodiments 1) to 4), wherein Ar 1 represents phenyl, which is di- or tri-substituted,

여기에서 치환기는 독립적으로 할로겐, 메틸, 및 시아노로부터 선택되며; wherein the substituents are independently selected from halogen, methyl, and cyano;

상기 치환기 중 적어도 하나는 상기 페닐의 메타- 또는 파라-위치에 부착되어 있다; At least one of the substituents is attached to the meta- or para-position of the phenyl;

≫ 특히, 존재하는 경우에, 상기 파라-위치의 치환기는 할로겐 또는 메틸이고; 및≫ In particular, when present, the substituent at the para- position is halogen or methyl; and

≫ 특히, 존재하는 경우에, 상기 메타-위치의 치환기는 할로겐이다.» In particular, when present, the substituent at the meta- position is halogen.

8) 또다른 실시형태는 실시형태 1) 내지 4) 중 어느 하나에 따른 화합물에 관한 것으로, Ar 1 은 페닐을 나타내며, 이는 이- 또는 삼-치환되며, 여기에서 치환기는 독립적으로 할로겐; 메틸; 및 시아노 (특히 할로겐 또는 메틸) 로부터 선택되며; 8) Another embodiment relates to a compound according to any one of embodiments 1) to 4), wherein Ar 1 represents phenyl, which is di- or tri-substituted, wherein the substituents are independently halogen; methyl; and cyano (especially halogen or methyl);

≫ 상기 페닐이 이-치환되는 경우에, 상기 치환기 중 적어도 하나는 메타-위치에 있으며, 상기 치환기는 특히 할로겐이고; 다른 치환기는 특히 다른 메타- 또는 파라-위치에 있거나; 또는≫ When the phenyl is di-substituted, at least one of the substituents is in the meta- position, and the substituent is in particular a halogen; Other substituents are in particular at different meta- or para- positions; or

≫ 상기 페닐이 삼-치환되는 경우에, 치환기는, Ar 1 의 부착 지점에 상대적으로, 2,3,4 또는 3,4,5 치환 패턴을 형성하며, 특히 파라-위치의 치환기는 할로겐 또는 메틸이고, 나머지 치환기는 독립적으로 할로겐 (특히 플루오로) 이다.≫ When the phenyl is tri-substituted, the substituents form a 2,3,4 or 3,4,5 substitution pattern, relative to the point of attachment of Ar 1 , especially the para- position substituent is halogen or methyl and the remaining substituents are independently halogen (especially fluoro).

9) 또다른 실시형태는 실시형태 1) 내지 4) 중 어느 하나에 따른 화합물에 관한 것으로, Ar 1 은 하기를 나타낸다9) Another embodiment relates to a compound according to any one of embodiments 1) to 4), wherein Ar 1 represents the following

. .

하위 실시형태에서, Ar 1 은 특히 군 A) 또는 B) 로부터 선택되는 기를 나타낸다:In a subembodiment, Ar 1 particularly represents a group selected from group A) or B):

여기에서 각각의 상기 군 A) 및 B) 는 특정 하위 실시형태를 형성한다.wherein each of the above groups A) and B) forms a specific sub-embodiment.

또다른 하위 실시형태에서, Ar 1 은 특히 군 C), D) 또는 E) 로부터 선택되는 기를 나타낸다:In another subembodiment, Ar 1 represents a group especially selected from groups C), D) or E):

여기에서 각각의 상기 군 C), D) 및 E) 는 특정 하위 실시형태를 형성한다.wherein each of the above groups C), D) and E) forms a specific sub-embodiment.

10) 또다른 실시형태는 실시형태 1) 내지 9) 중 어느 하나에 따른 화합물에 관한 것으로, R 1 은 메톡시를 나타낸다.10) Another embodiment relates to a compound according to any one of embodiments 1) to 9), wherein R 1 represents methoxy.

11) 또다른 실시형태는 실시형태 1) 내지 10) 중 어느 하나에 따른 화합물에 관한 것으로, L 은 직접 결합을 나타낸다.11) Another embodiment relates to the compound according to any one of embodiments 1) to 10), wherein L represents a direct bond.

12) 또다른 실시형태는 실시형태 1) 내지 11) 중 어느 하나에 따른 화합물에 관한 것으로, Ar 2 는 페닐을 나타내며, 이는 미치환, 일-, 이- 또는 삼-치환 (특히 일-, 또는 이-치환) 되며, 여기에서 치환기는 독립적으로 C1-6-알킬 (특히 메틸), C1-3-알콕시 (특히 메톡시), 할로겐, 및 시아노로부터 선택된다 (특히 상기 치환기 중 적어도 하나는 메타-위치에 있다).12) Another embodiment relates to a compound according to any one of embodiments 1) to 11), wherein Ar 2 represents phenyl, which is unsubstituted, mono-, di- or tri-substituted (in particular mono-, or di-substitution), wherein the substituents are independently selected from C 1-6 -alkyl (especially methyl), C 1-3 -alkoxy (especially methoxy), halogen, and cyano (especially at least one of the above substituents is in meta- position).

13) 또다른 실시형태는 실시형태 1) 내지 11) 중 어느 하나에 따른 화합물에 관한 것으로, Ar 2 는 페닐을 나타내며, 이는 일-, 또는 이-치환되며, 여기에서 치환기는 독립적으로 C1-4-알킬 (특히 메틸), C1-3-알콕시 (특히 메톡시), 할로겐, 및 시아노로부터 선택된다 (특히 상기 치환기 중 적어도 하나는 메타-위치에 있다).13) Another embodiment relates to a compound according to any one of embodiments 1) to 11), wherein Ar 2 represents phenyl, which is mono-, or di-substituted, wherein the substituents are independently C 1- 4 -alkyl (especially methyl), C 1-3 -alkoxy (especially methoxy), halogen, and cyano (in particular at least one of these substituents is in the meta- position).

14) 또다른 실시형태는 실시형태 1) 내지 11) 중 어느 하나에 따른 화합물에 관한 것으로, Ar 2 는 페닐을 나타내며, 이는14) Another embodiment relates to the compound according to any one of embodiments 1 ) to 11), wherein Ar 2 represents phenyl,

· 일-치환되며, 여기에서 치환기는 C1-4-알킬 (특히 메틸), C1-3-알콕시 (특히 메톡시), 할로겐, 및 시아노로부터 선택된다 (특히 상기 치환기는 메타-위치에 있다); 또는mono-substituted, wherein the substituent is selected from C 1-4 -alkyl (especially methyl), C 1-3 -alkoxy (especially methoxy), halogen, and cyano (in particular the substituent is in the meta- position there is); or

· 이-치환되며, 여기에서 치환기는 독립적으로 C1-4-알킬 (특히 메틸), C1-3-알콕시 (특히 메톡시), 할로겐, 및 시아노로부터 선택된다 (특히 상기 치환기는 메타-위치에 있다).· di-substituted, wherein the substituents are independently selected from C 1-4 -alkyl (especially methyl), C 1-3 -alkoxy (especially methoxy), halogen, and cyano (in particular the substituents are meta- location).

15) 또다른 실시형태는 실시형태 1) 내지 10) 중 어느 하나에 따른 화합물에 관한 것으로, 단편 -L-Ar 2 는 하기를 나타낸다:15) Another embodiment relates to the compound according to any one of embodiments 1) to 10), wherein the fragment - L - Ar 2 represents:

16) 본 발명은, 따라서, 실시형태 1) 에 정의된 바와 같은 식 (I) 의 화합물, 또는 그들 각각의 종속성의 고려 하에 실시형태 2) 내지 15) 중 어느 하나의 특징에 의해 추가로 한정되는 화합물; 이의 약학적으로 허용가능한 염; 및 본원에서 아래에서 추가로 기술되는 바와 같은 이러한 화합물의 용도에 관한 것이다. 의심을 피하기 위해, 특히 식 (I) 의 화합물에 관련되는 하기 실시형태가 그에 따라 가능하고 의도되며, 개별화된 형태로 구체적으로 개시된다:16) The invention is therefore further defined by compounds of formula (I) as defined in embodiment 1), or by the features of any one of embodiments 2) to 15), taking into account their respective dependencies. compound; pharmaceutically acceptable salts thereof; and the uses of such compounds as further described herein below. For the avoidance of doubt, the following embodiments, particularly relating to compounds of formula (I), are thereby possible and intended and are specifically disclosed in personalized form:

상기 목록에서 숫자는 상기 제공된 그의 번호매김에 따른 실시형태를 나타내는 한편, "+" 는 또 다른 실시형태로부터의 종속성을 표시한다. 상이한 개별화된 실시형태를 쉼표에 의해 분리한다. 다시 말해서, "11+9+4+1" 은, 예를 들어 실시형태 1) 을 인용하는 실시형태 4) 을 인용하는 실시형태 9) 을 인용하는 실시형태 11) 을 나타내며, 즉, 실시형태 "11+9+4+1" 은 실시형태 4), 9) 및 11) 의 모든 특징에 의해 추가로 한정되는, 실시형태 1) 에 따른 식 (I) 의 화합물에 상응한다.A number in the above list indicates an embodiment according to its numbering provided above, while a "+" indicates a dependency from another embodiment. Different individualized embodiments are separated by commas. In other words, "11+9+4+1" represents, for example, embodiment 11) which cites embodiment 9) which cites embodiment 4) which cites embodiment 1), that is, embodiment " 11+9+4+1" corresponds to the compound of formula (I) according to embodiment 1), which is further defined by all the features of embodiments 4), 9) and 11).

17) 본 발명의 추가의 양태는 실시형태 1) 에 따른 식 (I) 의 화합물에 관한 것으로, 이는 또한 식 (V) (식에서 절대 배치는 해당 식에 도시된 바와 같다고 이해된다) 의 화합물이다:17) A further aspect of the invention relates to compounds of formula (I) according to embodiment 1), which are also compounds of formula (V) (in which the absolute configuration is understood to be as shown in the formula):

식에서In Eq.

X 는 O 또는 NR 2 를 나타내며; 여기에서 R 2 는 수소, C1-3-알킬 (특히 메틸 또는 에틸), -CO-H, -SO2-C1-3-알킬 (특히 SO2-CH3), 또는 -CO-C1-3-알킬 (특히 -CO-CH3) 을 나타내고; X represents O or N R 2 ; where R 2 is hydrogen, C 1-3 -alkyl (especially methyl or ethyl), -CO-H, -SO 2 -C 1-3 -alkyl (especially SO 2 -CH 3 ), or -CO-C 1-3 -alkyl (especially -CO-CH 3 );

Ar 1 은 페닐을 나타내며, 이는 일-, 이-, 삼-, 사-, 또는 오-치환 (특히 이-, 또는 삼-치환) 되며, 여기에서 치환기는 독립적으로 할로겐; 메틸; 시아노; 및 메톡시로부터 선택되고 (특히 독립적으로 할로겐 및 메틸로부터 선택되고); Ar 1 represents phenyl, which is mono-, di-, tri-, tetra-, or penta-substituted (especially di-, or tri-substituted), wherein the substituents are independently halogen; methyl; cyano; and methoxy (especially independently selected from halogen and methyl);

[기 Ar 1 은 특히 실시형태 9) 또는 임의의 그것의 하위 실시형태에 나열된 기를 나타내고] [Group Ar 1 represents in particular a group listed in embodiment 9) or any sub-embodiment thereof]

R 1 은 하기를 나타내고 R 1 represents the following

· 히드록시; · hydroxy;

· C1-3-알콕시;· C 1-3 -alkoxy;

· -O-CO-C1-3-알킬; · -O-CO-C 1-3 -alkyl;

· -O-CH2-CH2-OH; 또는 · -O-CH 2 -CH 2 -OH; or

· -O-CH2-CO-OH; · -O-CH 2 -CO-OH;

[이러한 치환기 R 1 은 특히 C1-3-알콕시 (특히 메톡시) 를 나타내고][This substituent R 1 especially represents C 1-3 -alkoxy (especially methoxy)]

L 은 직접 결합 또는 메틸렌 (특히 직접 결합) 을 나타내고; 및 L represents a direct bond or methylene (especially a direct bond); and

Ar 2 는 하기를 나타낸다 Ar 2 represents

· 페닐, 상기 페닐은 미치환, 일-, 이- 또는 삼-치환 (특히 일-, 또는 이-치환) 되며, 여기에서 치환기는 독립적으로 메틸, 메톡시, 할로겐, 및 시아노로부터 선택됨;· Phenyl, wherein the phenyl is unsubstituted, mono-, di- or tri-substituted (especially mono- or di-substituted), wherein the substituents are independently selected from methyl, methoxy, halogen, and cyano;

실시형태 2) 내지 16) 에 개시된 특징은 실시형태 17) 에 따른 식 (V) 의 화합물에도 준용하여 적용되는 것이 의도된다.The features disclosed in embodiments 2) to 16) are intended to apply mutatis mutandis to the compound of formula (V) according to embodiment 17).

18) 또다른 실시형태 실시형태 1) 에 따른 식 (I) 의 화합물에 관한 것으로, 이는 하기 화합물로부터 선택된다:18) Another embodiment relates to a compound of formula (I) according to embodiment 1), which is selected from the following compounds:

(2R,3R,4S,5R,6R)-N-(3-클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran -3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran -2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydro furan-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H- Pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-N-(3-아이오도페닐)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-N-( 3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H- Pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetra hydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-클로로-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4- Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-시아노-5-메톡시페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-시아노-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-cyano-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-시아노-5-플루오로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3- triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro- 2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1, 2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3- triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro- 2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1, 2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N- (3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N- (3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1 ,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3- methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2 ,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1- yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2 -Carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole- 1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran -2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-tria Zol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H -pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole- 1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran -2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran -3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran -2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydro furan-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H- Pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-N-(3-아이오도페닐)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-N-( 3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H- Pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetra hydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-클로로-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4- Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-시아노-5-메톡시페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-시아노-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-cyano-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-시아노-5-플루오로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3-Bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3- triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro- 2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1, 2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3- triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro- 2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1, 2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N- (3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N- (3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1 ,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3- methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2 ,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1- yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2 -Carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole- 1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran -2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-tria Zol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H -pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole- 1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran -2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxyp rolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4 -Hydroxypyrrolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydride Roxypyrrolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidin-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3- triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidin-3-yl)-3-methoxytetrahydro- 2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidin-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1- yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidin-3-yl)-3-methoxytetrahydro-2H-pyran-2 -Carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxyp rolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4 -Hydroxypyrrolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydride Roxypyrrolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidin-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidin-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidin-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-5 -Hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-bromo-2 ,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디브로모페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dibromophenyl) -4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-5 -Hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-cyano Phenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole- 1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-bromo-2 ,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디브로모페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dibromophenyl) -4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dibromophenyl) -5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dibromophenyl) -5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-4 -(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-4 -(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-chloro-3, 5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3- methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-chloro-3, 5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3- methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-chloro-3, 5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-chloro-3, 5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-4 -(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H -pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-4 -(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H -pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-N-((3S,4S)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine-3 -yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole -1-yl)tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-N-((3S,4S)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidin-3-yl )-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1 -1) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-N-((3S,4S)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3,5-dichlorophenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidin-3-yl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-N-((3S,4S)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidin-3-yl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-N-((3R,4R)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidine-3 -yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole -1-yl)tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-N-((3R,4R)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidin-3-yl )-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1 -1) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-N-((3R,4R)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidin-3-yl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-N-((3S,4S)-4-히드록시-1-메틸피롤리딘-3-일)-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((3S,4S)-4-hydroxy-1-methylpyrrolidine -3-yl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-N-((3S,4S)-1-에틸-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-N-((3S,4S)-1-ethyl-4-hydroxypyrrolidin-3-yl) -5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-N-((3S,4S)-4-히드록시-1-(메틸술포닐)피롤리딘-3-일)-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((3S,4S)-4-hydroxy-1-(methylsulfonyl ) pyrrolidin-3-yl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-tria zol-1-yl)tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-3-hydroxytetra hydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-클로로-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-3- Hydroxytetrahydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-3 -Hydroxytetrahydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1 -1) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-3-hydride Roxytetrahydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl ) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-3-hydroxytetra hydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-3-hydride Roxytetrahydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl ) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시테트라히드로-2H-피란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxytetra hydro-2H-pyran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시테트라히드로-2H-피란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydride Roxytetrahydro-2H-pyran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl ) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시테트라히드로-2H-피란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxytetra hydro-2H-pyran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시테트라히드로-2H-피란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydride Roxytetrahydro-2H-pyran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl ) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-3-히드록시피페리딘-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-3-hydroxyp peridin-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-3-히드록시피페리딘-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-3 -Hydroxypiperidin-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-3-히드록시피페리딘-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-3-hydride Roxypiperidin-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-3-히드록시피페리딘-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-3-hydride Roxypiperidin-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피페리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxyp peridin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피페리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드; 및(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydride Roxypiperidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide; and

(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피페리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드.(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydride Roxypiperidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide.

실시형태 1) 내지 18) 에 따른 식 (I) 의 화합물 및 그의 약학적으로 허용가능한 염은 약제로서, 예를 들어 장 투여용 (특히 경구, 예를 들어 정제 또는 캡슐의 형태) 또는 비경구 투여용 (국소 적용 또는 흡입을 포함) 약학적 조성물의 형태로 사용될 수 있다.The compounds of formula (I) according to embodiments 1) to 18) and their pharmaceutically acceptable salts are used as medicaments, for example for enteral administration (especially oral, for example in the form of tablets or capsules) or parenteral administration. It can be used in the form of a pharmaceutical composition (including topical application or inhalation).

약학적 조성물의 제조는 기재된 식 (I) 의 화합물 또는 그의 약학적으로 허용가능한 염을, 선택적으로 다른 치료적으로 가치있는 물질과 조합으로, 적합한, 비독성, 불활성, 치료적으로 적합한 고체 또는 액체 담체 물질 및 원하는 경우 유용한 약학적 보조제와 함께 생약 투여 형태로 만듬으로써, 임의의 당업자에게 친숙할 방식으로 실행될 수 있다 (예를 들어 Remington, The Science and Practice of Pharmacy, 21st Edition (2005), Part 5, "Pharmaceutical Manufacturing" [published by Lippincott Williams & Wilkins] 참조).The preparation of pharmaceutical compositions involves mixing a compound of formula (I) described, or a pharmaceutically acceptable salt thereof, optionally in combination with other therapeutically valuable substances, in a suitable, non-toxic, inert, therapeutically suitable solid or liquid. This can be done in a manner that will be familiar to any person skilled in the art, by making herbal dosage forms with carrier substances and, if desired, useful pharmaceutical adjuvants (e.g. Remington, The Science and Practice of Pharmacy , 21st Edition (2005), Part 5 , “Pharmaceutical Manufacturing” [published by Lippincott Williams & Wilkins]).

본 발명은 또한 약학적 활성량의 실시형태 1) 내지 18) 에 따른 식 (I) 의 화합물을 대상체에게 투여하는 것을 포함하는, 본원에 언급된 질환 또는 장애의 예방 / 방지 또는 치료 방법에 관한 것이다. 본 발명의 하위 실시형태에서, 투여량은 1 일 당 1 mg 과 1000 mg 사이로 포함된다.The invention also relates to a method for preventing/preventing or treating a disease or disorder mentioned herein, comprising administering to a subject a pharmaceutically active amount of a compound of formula (I) according to embodiments 1) to 18). . In a sub-embodiment of the invention, the dosage is comprised between 1 mg and 1000 mg per day.

의심의 여지를 피하기 위해, 화합물이 특정한 질환의 예방 / 방지 또는 치료에 유용하다고 기재되는 경우, 이러한 화합물은 마찬가지로 상기 질환의 예방 / 방지 또는 치료용 약제의 제조에 사용하는데 적합하다. 마찬가지로, 이러한 화합물은 또한 이러한 화합물의 유효량을, 이를 필요로 하는 대상체 (포유동물, 특히 인간) 에게 투여하는 것을 포함하는, 이러한 질환의 예방 / 방지 또는 치료 방법에 적합하다.For the avoidance of doubt, where a compound is described as being useful for the prevention/prevention or treatment of a particular disease, such compound is likewise suitable for use in the manufacture of a medicament for the prevention/prevention or treatment of said disease. Likewise, these compounds are also suitable for methods of prophylaxis/prevention or treatment of these diseases, comprising administering an effective amount of these compounds to a subject in need thereof (a mammal, especially a human).

19) 또다른 실시형태는 천연 리간드에 대한 갈렉틴-3 결합과 관련되는 질환 및 장애의 예방 / 방지 또는 치료에 유용한 실시형태 1) 내지 18) 중 어느 하나에 정의된 바와 같은 식 (I) 의 화합물에 관한 것이다.19) Another embodiment is a method of formula (I) as defined in any one of embodiments 1) to 18) useful for the prevention/prevention or treatment of diseases and disorders associated with galectin-3 binding to natural ligands. It's about compounds.

천연 리간드에 결합하는 Gal-3 과 관련되는 이러한 질환 및 장애는 특히 Gal-3 의 생리학적 활성의 저해가 유용한 질환 및 장애, 예컨대 Gal-3 수용체가 참여하거나, 질환의 병인 또는 병리학에 관여하거나, 또는 질환의 적어도 하나의 증상과 연관되는 질환이다.These diseases and disorders associated with Gal-3 binding to natural ligands are particularly useful in diseases and disorders in which inhibition of the physiological activity of Gal-3 is useful, such as in which the Gal-3 receptor participates or is involved in the etiology or pathology of a disease; Or it is a disease that is associated with at least one symptom of the disease.

천연 리간드에 대한 갈렉틴-3 결합과 관련되는 질환 또는 장애 특히 하기를 포함하는 것으로서 정의될 수 있다:A disease or disorder associated with galectin-3 binding to its natural ligand may be defined as comprising, in particular:

ㆍ 하기를 포함하는 기관의 섬유증:dot Fibrosis of organs including:

≫ 모든 형태의 섬유화 간질성 폐 질환, 특히 특발성 폐 섬유증 (대안적으로는 잠복성 섬유화 폐포염으로 명명); 전신 염증성 질환 예컨대 류마티스 관절염, 경피증 (전신 경화증, SSc), 루푸스 (전신 홍반성 루푸스, SLE), 다발성근염 또는 혼합 결합 조직 질환 (MCTD) 에 2 차적인 폐 섬유증; 사르코이드증에 2 차적인 폐 섬유증; 방사선-유도된 섬유증을 포함하는 의원성 폐 섬유증; 규폐증-유도된 폐 섬유증; 석면-유도된 폐 섬유증; 및 흉막 섬유증을 포함하는, 모든 형태의 허파 / 폐 섬유증; ≫ All forms of fibrosing interstitial lung disease, especially idiopathic pulmonary fibrosis (alternatively named cryptogenic fibrosing alveolitis); Pulmonary fibrosis secondary to systemic inflammatory diseases such as rheumatoid arthritis, scleroderma (systemic sclerosis, SSc), lupus (systemic lupus erythematosus, SLE), polymyositis or mixed connective tissue disease (MCTD); Pulmonary fibrosis secondary to sarcoidosis; Iatrogenic pulmonary fibrosis, including radiation-induced fibrosis; silicosis-induced pulmonary fibrosis; asbestos-induced pulmonary fibrosis; and all forms of lung/pulmonary fibrosis, including pleural fibrosis;

≫ 만성 신장 질환 (CKD), (급성 또는 만성) 신부전, 세관사이질 신염, 및/또는 만성 신증 예컨대 (특발성) 사구체신염 및 SLE 또는 SSc 과 같은 전신 염증성 질환, 당뇨병, 초점성 분절성 사구체 경화증, IgA 신장병증, 고혈압, 신장 동종이식편 및 알포트 증후군에 2 차적인 사구체신염에 의해 초래되는 / 이와 연관되는 신장 섬유증을 포함하는, 신장 / 신 섬유증; ≫ Chronic kidney disease (CKD), renal failure (acute or chronic), tubulointerstitial nephritis, and/or chronic nephropathy such as (idiopathic) glomerulonephritis and systemic inflammatory diseases such as SLE or SSc, diabetes mellitus, focal segmental glomerulosclerosis, IgA nephropathy Kidney/renal fibrosis, including renal fibrosis caused by/associated with glomerulonephritis secondary to glomerulonephritis, hypertension, renal allograft and Alport syndrome;

≫ 간경변증, 알코올-유도된 간 섬유증, 비알코올성 지방간염, 담관 손상, 원발성 담즙성 간경변증 (원발성 경화성 담관염으로도 공지됨), 감염- 또는 바이러스-유도된 간 섬유증 (예를 들어 만성 HCV 감염) 및 자가면역 간염을 포함하는, 모든 형태의 간 / 간성 섬유증 (문맥 고혈압과 연관되거나 연관되지 않음); ≫ Cirrhosis, alcohol-induced liver fibrosis, non-alcoholic steatohepatitis, bile duct injury, primary biliary cirrhosis (also known as primary sclerosing cholangitis), infection- or virus-induced liver fibrosis (e.g. chronic HCV infection) and autologous All forms of liver/hepatic fibrosis (with or without associated portal hypertension), including immune hepatitis;

≫ 심혈관 질환, 심부전, 파브리병, CKD; 당뇨병, 고혈압 또는 고콜레스테롤혈증과 연관되는 심 / 심장 섬유증을 포함하는, 모든 형태의 심 / 심장 섬유증; ≫ Cardiovascular disease, heart failure, Fabry disease, CKD; All forms of cardiac/cardiac fibrosis, including cardiac/cardiac fibrosis associated with diabetes, hypertension, or hypercholesterolemia;

≫ SSc 에 2 차적인 장 섬유증 및 방사선-유도된 장 섬유증을 포함하는 장 섬유증; ≫ intestinal fibrosis, including intestinal fibrosis secondary to SSc and radiation-induced intestinal fibrosis;

≫ SSc 및 피부 반흔을 포함하는 피부 섬유증; ≫ Skin fibrosis, including SSc and skin scarring;

≫ 방사선-유도된 두경부 섬유증을 포함하는 두경부 섬유증; ≫ Head and neck fibrosis, including radiation-induced head and neck fibrosis;

≫ 반흔을 포함하는 눈 / 각막 섬유증 (예를 들어 레이저 각막절삭가공성형술 또는 섬유주절제술의 후유증); ≫ Eye/corneal fibrosis, including scarring (e.g. sequelae of laser keratoplasty or trabeculectomy);

≫ 화상-유도된 또는 수술적 비후성 반흔 및 켈로이드를 포함하는 비후성 반흔 및 켈로이드; ≫ Hypertrophic scars and keloids, including burn-induced or surgical hypertrophic scars and keloids;

≫ 장기 이식의 섬유증 후유증 (각막 이식 포함); 및 ≫ Fibrotic sequelae of organ transplantation (including corneal transplantation); and

≫ 자궁내막증, 척수 섬유증, 골수섬유증, 혈관주위 및 동맥 섬유증; 및 반흔 조직의 형성, 페로니병, 복부 또는 장 유착, 방광 섬유증, 비강 섬유증 및 섬유아세포에 의해 매개되는 섬유증을 포함하는, 다른 섬유성 질환; ≫ endometriosis, spinal fibrosis, myelofibrosis, perivascular and arterial fibrosis; and other fibrotic diseases, including formation of scar tissue, Peyronie's disease, abdominal or intestinal adhesions, bladder fibrosis, nasal fibrosis and fibroblast-mediated fibrosis;

ㆍ 급성 및 만성 바이러스 간염; 관절염 및 혈관염에 의해 초래된 / 이와 연관된 간경변증; 관절염, 심근염, 당뇨병 또는 신경학적 증상에 의해 초래된 / 이와 연관된 대사성 간 질환; 고지혈증, 염증성 장 질환 (IBD) 또는 궤양성 대장염에 의해 초래된 / 이와 연관된 담즙울체성 질환; 간 종양; 셀리악병, 자가면역 용혈성 빈혈, IBD, 자가면역 갑상선염, 궤양성 대장염, 당뇨병, 사구체신염, 심막염, 자가면역 갑상선염, 갑상선 기능항진증, 다발성근염, 쇼그렌 증후군, 지방층염, 폐포염 또는 알코올성 지방증에 의해 초래된 / 이와 연관된 자가면역 간염 및 간경변증; 치매와 연관된 간경변증; 말초 신경병증과 연관된 간경변증; 구강 또는 식도 암에 의해 초래된 / 이와 연관된 간경변증; 비만, 대사 증후군 또는 제 2 형 당뇨병에 의해 초래된 / 이와 연관된 비-알코올성 지방간 질환 (특히 비-알코올성 지방간염); 간 혈관 장애 (버드-키아리 증후군, 간문맥 혈전증, 굴맥관 폐쇄 증후군 포함); 급성 및 만성 간부전 (문맥 고혈압과 연관되거나 연관되지 않음); 간 기능저하를 포함하는, (급성 또는 만성) 간 질환 및 장애; dot Acute and chronic viral hepatitis; Cirrhosis caused by/related to arthritis and vasculitis; Metabolic liver disease caused by/related to arthritis, myocarditis, diabetes, or neurological conditions; Cholestatic disease caused by/related to hyperlipidemia, inflammatory bowel disease (IBD), or ulcerative colitis; liver tumor; Caused by celiac disease, autoimmune hemolytic anemia, IBD, autoimmune thyroiditis, ulcerative colitis, diabetes, glomerulonephritis, pericarditis, autoimmune thyroiditis, hyperthyroidism, polymyositis, Sjogren's syndrome, panniculitis, alveolitis, or alcoholic steatosis. Caused by/related to autoimmune hepatitis and cirrhosis; Cirrhosis associated with dementia; Cirrhosis associated with peripheral neuropathy; Cirrhosis caused by/related to oral or esophageal cancer; Non-alcoholic fatty liver disease (particularly non-alcoholic steatohepatitis) caused by/related to obesity, metabolic syndrome or type 2 diabetes; Hepatic vascular disorders (including Budd-Chiari syndrome, portal vein thrombosis, sinusoidal obstruction syndrome); Acute and chronic liver failure (with or without associated portal hypertension); Liver diseases and disorders (acute or chronic), including liver failure;

ㆍ 급성 신장 손상 및 만성 신장 질환 (CKD) [특히, 신장 질환을 개선하는 세계적 결과물 (Kidney Disease Improving Global Outcomes) (KDIGO) 가이드라인에 의해 정의된 바와 같은 병기 1 내지 5 의 CKD], 특히 심장 질환에 의해 초래된 / 이와 연관된 (심장-신장 증후군 제 1 형 및 제 2 형으로도 지칭함), 또는 고혈압에 의해 초래된 / 이와 연관된, 또는 당뇨병에 의해 초래된 / 이와 연관된 (고혈압과 연관된 DKD 를 포함하여, 당뇨병성 신장 질환 (DKD) 으로도 지칭함) (여기서 이러한 당뇨병은 특히 제 1 형 또는 제 2 형 당뇨병임), 또는 염증성 질환 및 장애에 의해 초래된 / 이와 연관된 (예컨대 사구체신염, 및 전신 염증성 질환 예컨대 SLE 또는 SSc, 간질성 신염, 혈관염, 패혈증, 요로 감염에 2 차적인 사구체신염), 또는 다낭성 신장 질환에 의해 초래된 / 이와 연관된, 또는 폐쇄성 신장병증에 의해 초래된 / 이와 연관된 (결석, 양성 전립선 비대증, 전립선 암, 후복막 골반 종양 포함), 또는 신경병성 방광 질환과 연관된 증후군에 의해 초래된 / 이와 연관된, CKD (특히 이들 병기의); 뿐만 아니라 급성 및 만성 신부전;dot Acute kidney injury and chronic kidney disease (CKD) [especially CKD stages 1 to 5 as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines], especially heart disease caused by/related to diabetes (also referred to as cardio-renal syndrome types 1 and 2), or caused by/related to high blood pressure, or caused by/related to diabetes (including DKD associated with hypertension) , also referred to as diabetic kidney disease (DKD), where such diabetes is especially type 1 or type 2 diabetes, or caused by/associated with inflammatory diseases and disorders (such as glomerulonephritis, and systemic inflammatory diseases) caused by/associated with polycystic kidney disease (e.g., SLE or SSc, interstitial nephritis, vasculitis, sepsis, glomerulonephritis secondary to urinary tract infection), or caused by/associated with obstructive nephropathy (stones, benign CKD (especially in these stages), caused by/associated with syndromes associated with benign prostatic hyperplasia, prostate cancer, retroperitoneal pelvic tumors), or neuropathic bladder disease; as well as acute and chronic renal failure;

ㆍ 고혈압, 고콜레스테롤혈증, 당뇨병, 염증, 비만, 고령/연령에 의해 초래된 / 이와 연관된 죽상동맥경화증; 고혈압, 고콜레스테롤혈증, 당뇨병, 고령/연령 에 의해 초래된 / 이와 연관된 말초 동맥 질환; 심부정맥 혈전증; 비만 또는 암에 의해 초래된 / 이와 연관된 폐색전증; 고령/연령, 고혈압, 마판 증후군, 선천 심장 질환, 염증성 또는 감염성 장애에 의해 초래된 / 이와 연관된 대동맥류 및 박리; 고혈압, 심방 세동, 고콜레스테롤혈증, 당뇨병, 고령/연령에 의해 초래된 / 이와 연관된 뇌혈관 질환; 고혈압, 고콜레스테롤혈증, 당뇨병, 고령/연령, 또는 CKD (특히, 신장 질환을 개선하는 세계적 결과물 (Kidney Disease Improving Global Outcomes) (KDIGO) 가이드라인에 의해 정의된 바와 같은 병기 1 내지 5 의 CKD) 에 의해 초래된 / 이와 연관된 관상 동맥성 심장 질환; 박테리아 감염에 의해 초래된 / 이와 연관된 류마티스성 심장 질환; 심장 및 혈관 종양; 심근증 및 부정맥증; 판막성 심장 질환 (판막 석회화 및 퇴행성 대동맥 협착증 포함); 감염, 심부전증, 사구체신염, 암에 의해 초래된 / 이와 연관된 염증성 심장 질환; 특히 울혈성 HF, 특히 수축기 HF / 감소된 박출 계수를 갖는 HF (HFrEF), 및 이완기 HF / 보존된 박출 계수를 갖는 HF (HFpEF) 를 포함하는 것으로서 정의되는 심부전 (HF) 을 포함하는, 심혈관 질환 및 장애;dot Hypertension, hypercholesterolemia, diabetes, inflammation, obesity, advanced age/age-induced/related atherosclerosis; Hypertension, hypercholesterolemia, diabetes, advanced age/peripheral arterial disease caused by/related to age; deep vein thrombosis; Pulmonary embolism caused by/related to obesity or cancer; Aortic aneurysms and dissections caused by/related to advanced age/age, hypertension, Marfan syndrome, congenital heart disease, inflammatory or infectious disorders; Hypertension, atrial fibrillation, hypercholesterolemia, diabetes, advanced age/cerebrovascular disease caused by/related to age; Hypertension, hypercholesterolemia, diabetes, advanced age/old age, or CKD (especially CKD stages 1 to 5 as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines) Coronary heart disease caused by/related to; Rheumatic heart disease caused by/related to bacterial infection; Heart and vascular tumors; cardiomyopathy and arrhythmias; Valvular heart disease (including valvular calcification and degenerative aortic stenosis); Inflammatory heart disease caused by/related to infection, heart failure, glomerulonephritis, cancer; Cardiovascular diseases, including heart failure (HF), especially defined as comprising congestive HF, especially systolic HF/HF with reduced ejection fraction (HFrEF), and diastolic HF/HF with preserved ejection fraction (HFpEF) and disability;

ㆍ 간질성 폐 질환 및 장애 (흡연-관련 간질성 폐 질환; 만성 폐쇄성 폐 질환과 연관된 / 이에 의해 초래된 간질성 폐 질환; 콜라겐 혈관 질환과 연관된 간질성 폐렴 (통상의 간질성 폐렴 포함), 또는 폐렴 포함);dot Interstitial lung diseases and disorders (smoking-related interstitial lung disease; interstitial lung disease associated with/caused by chronic obstructive pulmonary disease; interstitial pneumonia associated with collagen vascular disease (including common interstitial pneumonia), or pneumonia include);

ㆍ 세포 증식성 질환 및 암 (고형 종양, 고형 종양 전이, 암종, 육종, 골수종 (및 다발성 골수종), 백혈병, 림프종, 혼합 유형의 암, 혈관 섬유종, 카포시 육종, 만성 림프구성 백혈병 (CLL), 척수 종양 및 암 세포의 침습성 전이 포함; 특히 상기 세포 증식성 질환 및 암은 갑상선, 중추신경계, 혀, 유방, 위장관, 두경부 편평세포, 췌장, 방광, 신장, 간, 부갑상선 또는 침샘의 암; 또는 림프종; 암종, 비소세포 폐암, 흑색종 또는 신경모세포종이다);dot Cell proliferative diseases and cancers (solid tumors, solid tumor metastases, carcinoma, sarcoma, myeloma (and multiple myeloma), leukemia, lymphoma, mixed types of cancer, angiofibroma, Kaposi's sarcoma, chronic lymphocytic leukemia (CLL), spinal tumor and invasive metastasis of cancer cells; in particular, the above cell proliferative diseases and cancers include cancer of the thyroid gland, central nervous system, tongue, breast, gastrointestinal tract, head and neck squamous cell, pancreas, bladder, kidney, liver, parathyroid gland or salivary gland; or lymphoma; carcinoma , non-small cell lung cancer, melanoma, or neuroblastoma);

ㆍ 만성 및 급성 염증성 및 자가면역 질환 및 장애 (특히 패혈증, Q-열, 천식, 류마티스 관절염, 다발성 경화증, SLE, SSc, 다발성근염, 판상 건선 (NASH 에 의해 초래된 / 이와 연관된 건선 포함), 아토피성 피부염, 염증성 신 / 신장 질환 예컨대 신장병증 (당뇨병성 신장병증, 사구체신염, 세관사이질 신염 포함), 염증성 심 / 심장 질환, 염증성 폐 / 폐 관련 질환; 염증성 간 / 간 관련 질환; 당뇨병 (제 1 형 또는 제 2 형) 및 당뇨병 관련 질환 예컨대 당뇨병성 혈관병증, 당뇨병성 신장병증, 당뇨병성 망막병증, 당뇨병성 말초 신경병증 또는 피부 관련 병상; 바이러스성 뇌염; 및 COVID-19 및 이의 후유증 포함) 를 포함하는, 염증성 및 자가면역 질환 및 장애;dot Chronic and acute inflammatory and autoimmune diseases and disorders (especially sepsis, Q-fever, asthma, rheumatoid arthritis, multiple sclerosis, SLE, SSc, polymyositis, plaque psoriasis (including psoriasis caused by/associated with NASH), atopic Dermatitis, inflammatory kidney/kidney diseases such as nephropathy (including diabetic nephropathy, glomerulonephritis, tubulointerstitial nephritis), inflammatory heart/cardiac disease, inflammatory lung/lung-related disease; inflammatory liver/liver-related disease; diabetes mellitus (Chapter 1) type or type 2) and diabetes-related diseases such as diabetic angiopathy, diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy or skin-related conditions; viral encephalitis; and COVID-19 and its sequelae) Inflammatory and autoimmune diseases and disorders, including;

ㆍ 위장관 질환 및 장애 (과민성 대장 증후군 (IBS), 염증성 장 질환 (IBD), 위염 및 비정상적 췌장 분비 포함);dot Gastrointestinal diseases and disorders (including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), gastritis, and abnormal pancreatic secretion);

ㆍ 췌장 질환 및 장애 (예를 들어 낭포성 섬유증과 연관된 췌장염 포함);dot Pancreatic diseases and disorders (including, for example, pancreatitis associated with cystic fibrosis);

ㆍ 비정상적 혈관형성 관련 질환 및 장애 (동맥 폐색 포함);dot Diseases and disorders associated with abnormal angiogenesis (including arterial occlusion);

ㆍ 뇌 관련 질환 및 장애 (뇌졸중 및 뇌출혈 포함); dot Brain-related diseases and disorders (including stroke and cerebral hemorrhage);

ㆍ 신경병성 통증 및 말초 신경병증; dot Neuropathic pain and peripheral neuropathy;

ㆍ 안구 질환 및 장애 (안구 건조 질환 (안구 건조 증후군), 황반변성 (노화 관련 AMD), 당뇨병 관련 질환 (당뇨병성 망막병증), 증식성 유리체망막병증 (PVR), 반흔성 유사천포창, 및 녹내장 (상승한 안압과 연관된 녹내장, 및 녹내장 여과 수술 후 안구 반흔 포함), 및 각막 혈관형성/혈관신생 포함); 및dot Eye diseases and disorders (dry eye disease (dry eye syndrome), macular degeneration (age-related AMD), diabetes-related disease (diabetic retinopathy), proliferative vitreoretinopathy (PVR), cicatricial pemphigoid, and glaucoma (elevated (including glaucoma associated with intraocular pressure, and ocular scarring after glaucoma filtration surgery), and corneal angiogenesis/angiogenesis); and

ㆍ 신장, 간, 심장, 폐, 췌장, 각막 및 피부와 같은 이식된 장기의 거부를 포함하는 이식 거부증; 조혈 줄기 세포 이식에 의해 야기된 이식편대숙주 질환; 만성 동종이식 거부증 및 만성 동종이식 혈관병; 및 이러한 이식 거부증의 후유증.dot Transplant rejection, which includes rejection of transplanted organs such as kidney, liver, heart, lung, pancreas, cornea, and skin; Graft-versus-host disease caused by hematopoietic stem cell transplantation; chronic allograft rejection and chronic allograft vascular disease; and the sequelae of such transplant rejection.

20) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 간 / 간장 섬유증, 신 / 신장 섬유증, 폐 / 허파 섬유증, 심 / 심장 섬유증, 안구 / 각막 섬유증 및 피부 섬유증; 뿐만 아니라 장 섬유증, 두경부 섬유증, 비후성 반흔 및 켈로이드; 및 장기 이식의 섬유증 후유증을 포함하는 기관의 섬유증의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.20) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), said compounds being used in liver/hepatic fibrosis, renal/kidney fibrosis, lung/pulmonary fibrosis, heart/cardiac fibrosis, eye / Corneal fibrosis and skin fibrosis; as well as intestinal fibrosis, head and neck fibrosis, hypertrophic scarring and keloids; and for use in the prevention/prevention or treatment of fibrosis of organs, including fibrosis sequelae of organ transplantation.

21) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 심혈관 질환 및 장애의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.21) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), wherein said compounds are for use in the prevention/prevention or treatment of cardiovascular diseases and disorders.

22) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 급성 신장 손상 및 만성 신장 질환 (CKD) 의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.22) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), wherein said compounds are for use in the prevention/prevention or treatment of acute kidney injury and chronic kidney disease (CKD) .

23) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 (급성 또는 만성) 간 질환 및 장애의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.23) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), which compounds are for use in the prevention / prevention or treatment of liver diseases and disorders (acute or chronic).

24) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 간질성 폐 질환 및 장애의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.24) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), wherein said compounds are for use in the prevention/prevention or treatment of interstitial lung diseases and disorders.

25) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 안구 질환 및 장애의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.25) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), wherein said compounds are for use in the prevention/prevention or treatment of ocular diseases and disorders.

26) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 세포 증식성 질환 및 암의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.26) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), wherein said compounds are for use in the prevention/prevention or treatment of cell proliferative diseases and cancer.

특히 이러한 세포 증식성 질환 및 암은 특히 상기 세포 증식성 질환 및 암은 갑상선, 중추신경계, 혀, 유방, 위장관, 두경부 편평세포, 췌장, 방광, 신장, 간, 부갑상선 또는 침샘의 암; 또는 림프종; 암종, 비소세포 폐암, 흑색종 또는 신경모세포종이다.In particular, these cell proliferative diseases and cancers include cancer of the thyroid gland, central nervous system, tongue, breast, gastrointestinal tract, head and neck squamous cell, pancreas, bladder, kidney, liver, parathyroid gland or salivary gland; or lymphoma; Carcinoma, non-small cell lung cancer, melanoma, or neuroblastoma.

27) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 만성 또는 급성 염증성 및 자가면역 질환 및 장애의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.27) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), wherein said compounds are for use in the prevention / prevention or treatment of chronic or acute inflammatory and autoimmune diseases and disorders .

28) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 위장관 질환 및 장애의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.28) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), wherein said compounds are for use in the prevention/prevention or treatment of diseases and disorders of the gastrointestinal tract.

29) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 췌장 질환 및 장애의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.29) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), wherein said compounds are for use in the prevention/prevention or treatment of pancreatic diseases and disorders.

30) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 비정상적 혈관형성 관련 질환 및 장애의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.30) A further embodiment relates to a compound of formula (I) for the use according to embodiment 19), wherein said compound is for use in the prevention/prevention or treatment of diseases and disorders associated with abnormal angiogenesis.

31) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 뇌 관련 질환 및 장애의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.31) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), wherein said compounds are for use in the prevention/prevention or treatment of brain-related diseases and disorders.

32) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 신경병성 통증 및 말초 신경병증의 예방 / 방지 또는 치료에서 사용하기 위한 것이다.32) A further embodiment relates to compounds of formula (I) for the use according to embodiment 19), wherein said compounds are for use in the prevention/prevention or treatment of neuropathic pain and peripheral neuropathy.

33) 추가의 실시형태는 실시형태 19) 에 따른 용도를 위한 식 (I) 의 화합물에 관한 것으로, 상기 화합물은 이식 거부증의 치료에서 사용하기 위한 것이다.33) A further embodiment relates to a compound of formula (I) for the use according to embodiment 19), wherein said compound is for use in the treatment of transplant rejection.

게다가, 식 (I) 의 화합물 (화합물 그 자체, 이의 염, 화합물 또는 이의 염을 함유하는 조성물, 또는 화합물 또는 이의 염의 용도 등에 상관 없이) 에 대해 제시된 임의의 선호도 및 (하위-)실시형태는 식 (II), (III), (IV), (IS), (IIS), (IIIS), (IVS), (IR), (IIR), (IIIR), (IVR) 및 (V) 의 화합물에 대해서도 준용하여 적용된다. Moreover, any preferences and (sub-)embodiments given for the compounds of formula (I) (whether the compounds themselves, salts thereof, compositions containing the compounds or salts thereof, or uses of the compounds or salts thereof, etc.) (II), (III), (IV), (I S ), (II S), (III S ), (IV S ), (I R ), (I R ), (III R ) , (IV R ) and (V) are also applied mutatis mutandis.

식 (I) 의 화합물의 제조:Preparation of compounds of formula (I):

식 (I) 의 화합물은 충분히 공지된 문헌 방법, 하기에 주어진 방법, 하기 실험 부분에 주어진 방법 또는 유사한 방법에 의해 제조될 수 있다. 최적 반응 조건은 사용되는 특정한 반응물 또는 용매에 따라 달라질 수 있지만, 이러한 조건은 일상적인 최적화 절차에 의해, 당업자에 의해 결정될 수 있다. 일부 경우에 있어서, 하기의 반응식 및/또는 반응 단계를 수행하는 순서는 반응을 촉진하거나, 또는 원치 않는 부산물을 피하기 위해서 변경될 수 있다. 하기에서 설명하는 일반적인 반응 순서에서, 정수 n 및 m 및 일반적인 기 R 1 , L, Ar 1 , Ar 2 , n 및 m 은 식 (I) 에 대해 정의된 바와 같다. 본원에서 사용되는 다른 약어는 명백하게 정의되거나, 실험 부문에서 정의되는 바와 같다. 일부 경우에서, 일반적인 기 R 1 , L, Ar 1 , Ar 2 , n 및 m 은 하기의 반응식에서 예시하는 조합과 양립할 수 없으며, 따라서 보호기 (Pg) 의 사용을 필요로 할 것이다. 보호기의 사용은 당업계에 잘 알려져 있다 (예를 들어 "Protective Groups in Organic Synthesis", T.W. Greene, P.G.M. Wuts, Wiley-Interscience, 1999 참조). 이 논의의 목적을 위해, 이러한 보호기는 필요에 따라 존재한다고 가정될 것이다. 일부 경우에서, 최종 생성물은, 예를 들어 새로운 최종 생성물을 제공하기 위해서, 치환기의 조작에 의해 추가로 변형될 수 있다. 이들 조작은 당업자에게 통상적으로 공지된 환원, 산화, 알킬화, 아실화, 가수분해 및 전이 금속 촉매된 교차-커플링 반응을 포함하지만 이에 제한되지는 않는다. 수득된 화합물은 또한 자체 공지된 방식으로, 염, 특히 약학적으로 허용가능한 염으로 전환될 수 있다. Compounds of formula (I) can be prepared by well-known literature methods, the methods given below, the methods given in the experimental section below or similar methods. Optimal reaction conditions may vary depending on the specific reactants or solvents used, but such conditions can be determined by those skilled in the art by routine optimization procedures. In some cases, the reaction schemes below and/or the order in which reaction steps are performed may be altered to expedite the reaction or avoid unwanted by-products. In the general reaction sequence described below, the integers n and m and the general groups R 1 , L , Ar 1 , Ar 2 , n and m are as defined for formula (I). Other abbreviations used herein are explicitly defined or as defined in the experimental section. In some cases, the common groups R 1 , L , Ar 1 , Ar 2 , n and m are incompatible with the combinations illustrated in the schemes below and will therefore require the use of a protecting group (Pg). The use of protecting groups is well known in the art (see, for example, “Protective Groups in Organic Synthesis”, TW Greene, PGM Wuts, Wiley-Interscience, 1999). For the purposes of this discussion, it will be assumed that these protecting groups are present as needed. In some cases, the final product can be further modified, for example by manipulation of substituents, to provide a new final product. These operations include, but are not limited to, reduction, oxidation, alkylation, acylation, hydrolysis and transition metal catalyzed cross-coupling reactions commonly known to those skilled in the art. The obtained compounds can also be converted into salts, especially pharmaceutically acceptable salts, in a manner known per se.

본 발명의 식 (I) 의 화합물은 하기 개략화된 반응의 일반적인 순서에 따라 제조될 수 있다. 식 (I) 의 화합물을 이끌어내는 단지 소수의 합성 가능성이 기재된다. Compounds of formula (I) of the invention can be prepared following the general sequence of reactions outlined below. Only a few synthetic possibilities leading to compounds of formula (I) are described.

식 (I) 의 화합물은 R 이 수소, 적합한 보호기 (Pg) 또는 R1 (식 (I) 에서 정의한 바와 같음) 인 구조 1 의 화합물을 구조 2 의 화합물과 커플링시켜 구조 3 을 생성함으로써 제조된다. 커플링 반응은 DCM 또는 DMF 또는 이의 혼합물과 같은 적합한 용매 중, TEA 또는 DIPEA 와 같은 염기의 존재 하에, DCC, HOBT 또는 T3P 와 같은 표준 펩티드 커플링 조건을 사용하여 수행된다. 대안적으로, POCl3 은 염기로서 피리딘과 함께 사용될 수 있다. 구조 2 및 3 에서, Pg 는 당업자에게 충분히 공지된 아세틸, 트리메틸실릴 (TMS) 또는 tert-부틸 디메틸실릴 (TBS), 또는 벤질과 같은 적합한 보호기이다. 구조 1 의 위치 4 및 6 에서의 히드록시기는 이소프로필리덴, 벤질리덴 또는 비스-tert-부틸 실릴 기와 같은 시클릭 보호기로 보호될 수 있다. R 은 적합한 보호기 (Pg) 이거나, 기 OR 은 R 1 (식 (I) 에서 정의된 바와 같음) 에 상응한다. 이어서, 구조 3 의 화합물은 탈보호되어 식 (I) 의 화합물을 생성한다.Compounds of formula (I) are prepared by coupling a compound of structure 1, wherein R is hydrogen, a suitable protecting group (Pg) or R 1 (as defined in formula (I)), with a compound of structure 2 to yield structure 3 . The coupling reaction is performed using standard peptide coupling conditions such as DCC, HOBT or T3P, in the presence of a base such as TEA or DIPEA, in a suitable solvent such as DCM or DMF or mixtures thereof. Alternatively, POCl 3 can be used with pyridine as the base. In structures 2 and 3, Pg is a suitable protecting group such as acetyl, trimethylsilyl (TMS) or tert-butyl dimethylsilyl (TBS), or benzyl, which are well known to those skilled in the art. The hydroxy groups at positions 4 and 6 of Structure 1 may be protected with cyclic protecting groups such as isopropylidene, benzylidene or bis-tert-butyl silyl groups. R is a suitable protecting group ( Pg ), or the group O R corresponds to R 1 (as defined in formula (I)). The compound of structure 3 is then deprotected to yield the compound of formula (I).

Pg 가 아실 보호기를 나타내는 경우, 이러한 보호기는 THF, 디옥산 등과 같은 추가의 용매의 존재 또는 부재 하에 및 K2CO3, NaOH, LiOH 와 같은 염기의 존재 하에, 예를 들어 물 또는 알코올에 의해 표준 조건 하에서 절단될 수 있다. 이러한 보호기가 벤질 기를 나타내는 경우, 보호기는 메탄올, EA, THF 등, 또는 이의 혼합물 중, Pd/C, PtO2 와 같은 촉매의 존재 하에, 예를 들어 수소에 의해, 또는 DCM 과 같은 용매 중에서 BBr3 에 의해 절단될 수 있다. 이러한 보호기가 TMS 또는 TBS 인 경우, 보호기는 피리딘 중에서 TBAF 또는 HF 와 같은 불소 이온을 사용하여 절단된다. 대안적으로, 실릴 보호기는 rt 와 환류 사이의 온도에서 수성 AcOH 와 같은 온화한 산성 조건 하에서 제거된다. Pg 가 이소프로필리덴, 벤질리덴 및 비스-tert-부틸 실릴렌 기와 같은 시클릭 보호기인 경우, 절단은 수성 AcOH 또는 TFA 를 사용하여 산성 조건 하에 수행될 수 있다.If Pg represents an acyl protecting group, these protecting groups can be removed by means of water or alcohol, for example, in the presence or absence of additional solvents such as THF, dioxane, etc. and in the presence of bases such as K 2 CO 3 , NaOH, LiOH. Can be cut under certain conditions. When this protecting group represents a benzyl group, the protecting group is reacted with BBr 3 in methanol, EA, THF, etc., or mixtures thereof, in the presence of a catalyst such as Pd/C, PtO 2 , for example by hydrogen, or in a solvent such as DCM. It can be cut by . When this protecting group is TMS or TBS, the protecting group is cleaved using a fluorine ion such as TBAF or HF in pyridine. Alternatively, the silyl protecting group is removed under mildly acidic conditions such as aqueous AcOH at temperatures between rt and reflux. When Pg is a cyclic protecting group such as isopropylidene, benzylidene and bis-tert-butyl silylene groups, cleavage can be performed under acidic conditions using aqueous AcOH or TFA.

구조 1 의 화합물은 20 내지 100℃ 의 온도에서 수성 산성 (conc. HCl) 또는 염기성 (NaOH) 조건을 사용하여 구조 4 에서의 니트릴 작용기를 카르복실산으로 가수분해시킨 후, 유리 히드록실 기를 적절히 보호 또는 개질시킴으로써 제조된다. 구조 4 는 또한 THF 또는 DMF 와 같은 용매 중, CuI 및 DIPEA 의 존재 하에, 예를 들어 구조 5 의 화합물을 구조 6 의 화합물과 반응시킴으로써 수득되며 (Click Chemistry in Glycoscience: New Development and Strategies, 1st Edition, 2013, John Wiley& Sons), 대안적으로 반응은 THF 와 같은 용매 중에서 구리 코일을 사용하여 상업용 연속 흐름 반응기 (Vapourtec) 상에서 실행될 수 있다. 구조 6 의 화합물은 상업적으로 입수가능하거나, 당업자에게 공지된 절차에 따라서 제조될 수 있다 (Synthesis 2011, 22, 3604-3611). 구조 5 의 화합물은 당업자에게 충분히 공지된 방법을 통해 상응하는 굴로푸라노오스 유도체로부터 제조될 수 있다 (Carbohydrate Research 1994, 251, 33-67; Bioorg. Med. Chem. 2002, 10, 1911-2013).The compound of structure 1 is prepared by hydrolyzing the nitrile functional group in structure 4 to a carboxylic acid using aqueous acidic (conc. HCl) or basic (NaOH) conditions at a temperature of 20 to 100° C., followed by appropriate protection of the free hydroxyl group. Or it is manufactured by reforming. Structure 4 is also obtained, for example, by reacting a compound of structure 5 with a compound of structure 6 in the presence of CuI and DIPEA in a solvent such as THF or DMF ( Click Chemistry in Glycoscience: New Development and Strategies , 1st Edition, 2013 , John Wiley&Sons), alternatively the reaction can be run on a commercial continuous flow reactor (Vapourtec) using a copper coil in a solvent such as THF. Compounds of structure 6 are commercially available or can be prepared according to procedures known to those skilled in the art ( Synthesis 2011 , 22 , 3604-3611). Compounds of structure 5 can be prepared from the corresponding gulofuranose derivatives through methods well known to those skilled in the art ( Carbohydrate Research 1994 , 251 , 33-67; Bioorg. Med. Chem . 2002, 10, 1911-2013) .

구조 2 의 화합물은 표준 조건 하에 적합한 실릴계 보호기로 구조 7 의 화합물을 보호함으로써 수득된다. 구조 7 의 화합물은 3,6-디옥사바이시클로[3.1.0]헥산, tert-부틸 6-옥사-3-아자바이시클로[3.1.0]헥산-3-카르복실레이트, 1-(6-옥사-3-아자바이시클로[3.1.0]헥산-3-일)에탄-1-온, 3,7-디옥사바이시클로[4.1.0]헵탄 또는 tert-부틸 7-옥사-3-아자바이시클로[4.1.0]헵탄-3-카르복실레이트와 아민의 반응에 의해 수득된다.Compounds of structure 2 are obtained by protecting compounds of structure 7 with suitable silyl-based protecting groups under standard conditions. The compound of structure 7 is 3,6-dioxabicyclo[3.1.0]hexane, tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate, 1-(6- Oxa-3-azabicyclo[3.1.0]hexan-3-yl)ethan-1-one, 3,7-dioxabicyclo[4.1.0]heptane or tert-butyl 7-oxa-3-azabicycle Obtained by reaction of rho[4.1.0]heptane-3-carboxylate with amine.

구조 2 의 화합물은 구조 1 의 화합물과의 커플링을 위해 라세미 형태로 또는 분리된 거울상이성질체로서 사용된다. 구조 3 또는 식 I 의 부분입체이성질체 (탈보호 후) 는 당업자에게 널리 공지된 기법, 예컨대 비키랄 또는 키랄 정지상을 사용하는 키랄 분취용 HPLC 를 사용하여 분리된다. 키랄 분취용 HPLC 에 전형적으로 사용되는 비키랄 또는 키랄 정지상은 예를 들어 각각 Waters XBridge C18, 10 μm OBD, 30x75 mm, 또는 Daicel Chiralcel OZ-H (5um) 칼럼, Daicel Chiralcel OJ-H (5-10 μm) 칼럼, ChiralPak IC (5 μm) 칼럼 , ChiralPak ID (5 μm) 칼럼, ChiralPak IG (5 μm) 칼럼, ChiralPak IH (5 μm) 칼럼, ChiralPak IE (5 μm) 칼럼, ChiralPak AS-H (5 μm), AD-H (5 μm) 또는 IB (5 μm) 칼럼이다.Compounds of structure 2 are used in racemic form or as isolated enantiomers for coupling with compounds of structure 1. Diastereomers of structure 3 or formula I (after deprotection) are separated using techniques well known to those skilled in the art, such as chiral preparative HPLC using achiral or chiral stationary phases. Achiral or chiral stationary phases typically used in chiral preparative HPLC include, for example, Waters μm) column, ChiralPak IC (5 μm) column, ChiralPak ID (5 μm) column, ChiralPak IG (5 μm) column, ChiralPak IH (5 μm) column, ChiralPak IE (5 μm) column, ChiralPak AS-H (5 μm) column μm), AD-H (5 μm) or IB (5 μm) column.

키랄 HPLC 의 전형적인 조건은 0.8 내지 160 mL/분의 유속에서 용리액 A (CO2) 및 용리액 B (DCM/MeOH, MeCN/MeOH, MeCN/EtOH, EtOH 중 0.1% Et2NH, MeOH, EtOH, iPrOH) 의 등용매 혼합물이다. 일부 경우에, 구조 2 의 화합물의 거울상이성질체적으로 순수한 형태가 구조 1 의 화합물과의 아미드 커플링에 사용되어 각각 구조 3 및 식 I 의 화합물의 순수한 거울상이성질체를 전달한다.Typical conditions for chiral HPLC are eluent A (CO 2 ) and eluent B (DCM/MeOH, MeCN/MeOH, MeCN/EtOH, 0.1% Et 2 NH in EtOH, MeOH, EtOH, iPrOH) at flow rates from 0.8 to 160 mL/min. ) is an isocratic mixture of . In some cases, the enantiomerically pure form of the compound of Structure 2 is used for amide coupling with the compound of Structure 1 to deliver the enantiomerically pure form of the compound of Structure 3 and Formula I, respectively.

부분입체이성질체가 분리되지 않은 경우에, IC50 값은 부분입체이성질체의 혼합물에 대해 측정된다.In cases where diastereomers are not separated, IC 50 values are determined for mixtures of diastereomers.

실험 부분experimental part

하기 실시예는 본 발명을 설명하나, 그 범주를 전혀 제한하지 않는다. The following examples illustrate the invention, but do not limit its scope in any way.

모든 온도는 ℃ 로 기재된다. 시판 출발 물질은 추가 정제 없이 입수한 대로 사용했다. 달리 명시되지 않는 한, 모든 반응은 질소 또는 아르곤 분위기 하에 실행했다. 화합물은 실리카 겔 상에서 플래시 크로마토그래피 (Biotage, Redisep) 에 의해, prep TLC (Merck 사제의 TLC-플레이트, 실리카 겔 60 F254) 에 의해, 또는 분취용 HPLC 에 의해 정제했다. 본 발명에 기재된 화합물은 1H-NMR (Bruker Neo, 400 MHz Ultra ShieldTM 또는 Bruker Avance III HD, Ascend 500 MHz; 화학적 이동은 사용된 용매에 대한 ppm 으로 제공됨; 다중도: s = 단일항, d = 이중항, t = 삼중항, q = 사중항, quint = 오중항, hex = 육중항, hept = 칠중항, m = 다중항, br = 브로드, 커플링 상수는 Hz 로 제공됨) 및/또는 하기에서 설명하는 조건을 사용하는 LCMS (체류 시간 tR 은 분 (min) 으로 제공됨; 질량 스펙트럼에 대해 수득된 분자량은 g/mol 로 제공됨) 를 특징으로 한다.All temperatures are reported in °C. Commercial starting materials were used as received without further purification. Unless otherwise specified, all reactions were performed under nitrogen or argon atmosphere. The compounds were purified by flash chromatography on silica gel (Biotage, Redisep), by prep TLC (TLC-plate from Merck, silica gel 60 F 254 ) or by preparative HPLC. The compounds described in the invention are 1H -NMR (Bruker Neo, 400 MHz Ultra ShieldTM or Bruker Avance III HD, Ascend 500 MHz; chemical shifts are given in ppm relative to the solvent used; multiplicity: s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, hex = sextet, hept = septet, m = multiplet, br = broad, coupling constants are given in Hz) and/or in Characterized by LCMS (retention time t R is given in min; molecular weights obtained for mass spectra are given in g/mol) using the conditions described.

사용된 특성화 방법:Characterization methods used:

LC-MS 체류 시간은 하기의 용리 조건을 사용하여 수득했다: LC-MS retention times were obtained using the following elution conditions:

A) LC-MS (A):A) LC-MS (A):

Zorbax RRHD SB-Aq, 1.8 μm, 2.1x50 mm 칼럼을 40℃ 에서 온도조절했다. 2 개의 용리 용매는 하기와 같았다: 용매 A = 물 + 0.04% TFA; 용매 B = MeCN. 용리액 유속은 0.8 mL/분이었으며, 용리 시작으로부터 시간 t 의 함수에서의 용리 혼합물 비율의 특징을 하기 표에서 요약한다 (선형 구배가 2 개 연속 시점 사이에서 사용됨):A Zorbax RRHD SB-Aq, 1.8 μm, 2.1x50 mm column was temperature controlled at 40°C. The two elution solvents were: Solvent A = water + 0.04% TFA; Solvent B = MeCN. The eluent flow rate was 0.8 mL/min and the characteristics of the elution mixture ratio as a function of time t from the start of elution are summarized in the table below (a linear gradient was used between two successive time points):

검출: 210 nm 에서의 UV.Detection: UV at 210 nm.

이하 기재된 조건을 사용하여 분취용 LC-MS 의 정제를 수행했다. Purification by preparative LC-MS was performed using the conditions described below.

B) 분취용 LC-MS (I): B) Preparative LC-MS (I):

Zorbax 칼럼 (Zorbax Dr. Maisch, 5 μm, 30x75 mm) 을 사용했다. 2 개 용리 용매는 하기와 같았다: 용매 A = 물 + 물 중 포름산 용액 0.5%; 용매 B = MeCN. 용리액 유속은 75 mL/분이었으며, 용리 시작으로부터 시간 t 의 함수에서의 용리 혼합물 비율의 특징을 하기 표에서 요약한다 (선형 구배가 2 개 연속 시점 사이에서 사용됨): A Zorbax column (Zorbax Dr. Maisch, 5 μm, 30x75 mm) was used. The two elution solvents were: Solvent A = water + 0.5% formic acid solution in water; Solvent B = MeCN. The eluent flow rate was 75 mL/min and the characteristics of the elution mixture ratio as a function of time t from the start of elution are summarized in the table below (a linear gradient was used between two successive time points):

C) 분취용 LC-MS (II): C) Preparative LC-MS (II):

Waters 칼럼 (Waters XBridge C18, 10 μm OBD, 30x75 mm) 을 사용했다. 2 개 용리 용매는 하기와 같았다: 용매 A = 물 + 물 중 25% NH4OH 의 용액 0.5%; 용매 B = MeCN. 용리액 유속은 75 mL/분이었으며, 용리 시작으로부터 시간 t 의 함수에서의 용리 혼합물 비율의 특징을 하기 표에서 요약한다 (선형 구배가 2 개 연속 시점 사이에서 사용됨): A Waters column (Waters XBridge C18, 10 μm OBD, 30x75 mm) was used. The two elution solvents were: Solvent A = 0.5% solution of water + 25% NH4OH in water; Solvent B = MeCN. The eluent flow rate was 75 mL/min and the characteristics of the elution mixture ratio as a function of time t from the start of elution are summarized in the table below (a linear gradient was used between two successive time points):

검출 210 nm.Detection 210 nm.

약어 (본원에서 사용되는 바와 같음):Abbreviations (as used herein):

ABTS 2,2'-아지노-비스(3-에틸벤조티아졸린-6-술폰산ABTS 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid

Ac 아세틸 예컨대 AcOH = 아세트산Ac Acetyl such as AcOH = acetic acid

aq. 수성aq. Mercury

Bu 부틸 (예컨대 nBuLi = n-부틸 리튬 중)Bu butyl (e.g. n BuLi = n-butyl lithium)

Ca 약Ca approximately

CC 실리카 상 칼럼 크로마토그래피 CC Column chromatography on silica

conc. 농축conc. concentration

DCM 디클로로메탄DCM dichloromethane

DIPEA N-에틸 디이소프로필 아민DIPEA N -ethyl diisopropyl amine

DMF 디메틸포름아미드DMF Dimethylformamide

DMSO 디메틸술폭시드DMSO dimethyl sulfoxide

EA 에틸 아세테이트EA ethyl acetate

eq (몰) 당량(들)eq (molar) equivalent(s)

Et 에틸Et ethyl

EtOH 에탄올EtOH ethanol

Et2O 디에틸 에테르Et 2 O diethyl ether

Ex. 실시예Ex. Example

FC 플래시 크로마토그래피F.C. flash chromatography

h 시간(들)h time(s)

HOBt 1-히드록시벤조트리아졸 히드레이트HOBt 1-Hydroxybenzotriazole hydrate

HPLC 고성능 액체 크로마토그래피 HPLC High performance liquid chromatography

hv 고진공hv high vacuum

LC 액체 크로마토그래피 LC liquid chromatography

M 몰 농도 [mol L-1]M molar concentration [mol L -1 ]

Me 메틸Me methyl

MeCN 아세토니트릴MeCN Acetonitrile

MeOH 메탄올MeOH methanol

MS 질량분석법M.S. mass spectrometry

min 분(들)min minute(s)

N 노르말 농도N normal concentration

NaOH 수산화 나트륨NaOH sodium hydroxide

OD 광학 밀도O.D. optical density

o/n 밤새o/n Overnight

org. 유기org. abandonment

Pg 보호기Pg saver

Ph 페닐Ph phenyl

PTSA p-톨루엔술폰산PTSA p -toluenesulfonic acid

rt 실온 rt room temperature

sat. 포화sat. saturation

TBME tert-부틸메틸에테르TBME tert-butylmethyl ether

TBS tert-부틸디메틸실릴TBS tert-butyldimethylsilyl

tBu tert-부틸 = 3 차 부틸tBu tert-butyl = tertiary butyl

TEA 트리에틸아민TEAs Triethylamine

Tf 트리플루오로메탄술포네이트 tf Trifluoromethane sulfonate

TFA 트리플루오로아세트산TFA Trifluoroacetic acid

THF 테트라히드로푸란THF tetrahydrofuran

TMS 트리메틸실릴 TMS trimethylsilyl

T3P 프로필포스폰산 무수물 T3P Propylphosphonic Anhydride

tR 체류 시간t R residence time

A - 전구체 및 중간체의 제조A - Preparation of precursors and intermediates

구조 1 의 중간체의 제조Preparation of intermediates of structure 1

화합물의 합성을 위해 하기 전구체를 제조했다:The following precursors were prepared for the synthesis of the compound:

중간체 1: (3R,4S,5R,6R)-6-(아세톡시메틸)-4-아지도테트라히드로-2H-피란-2,3,5-트리일 트리아세테이트Intermediate 1: (3R,4S,5R,6R)-6-(acetoxymethyl)-4-azidotetrahydro-2H-pyran-2,3,5-triyl triacetate

(3R,4S,5R,6R)-6-(아세톡시메틸)-4-아지도테트라히드로-2H-피란-2,3,5-트리일 트리아세테이트를, Ref: Carbohydrate Research 1994, 251, 33-67 및 이에 인용된 참고문헌로부터의 문헌 절차에 따라 (3aR,5S,6S,6aR)-5-((R)-2,2-디메틸-1,3-디옥솔란-4-일)-2,2-디메틸테트라히드로푸로[2,3-d][1,3]디옥솔-6-올로부터 합성했다.(3R,4S,5R,6R)-6-(acetoxymethyl)-4-azidotetrahydro-2H-pyran-2,3,5-triyl triacetate, Ref: Carbohydrate Research 1994, 251, 33 (3aR,5S,6S,6aR)-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2 according to literature procedures from -67 and references cited therein. It was synthesized from 2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol.

중간체 2: (2R,3R,4R,5R,6S)-2-(아세톡시메틸)-6-시아노-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-3,5-디일 디아세테이트Intermediate 2: (2R,3R,4R,5R,6S)-2-(acetoxymethyl)-6-cyano-4-(4-(3,4,5-trifluorophenyl)-1H-1, 2,3-triazol-1-yl) tetrahydro-2H-pyran-3,5-diyl diacetate

중간체 1 (10000 mg, 26.5 mmol, 1 eq) 을 니트로메탄 (4 vol.) (40 mL) 에 용해하고, 트리메틸실릴 시아니드 98% (10.2 mL, 79.6 mmol, 3 eq) 및 보론 트리플루오라이드 디에틸 에테레이트 (3.93 mL, 31.8 mmol, 1.2 eq) 를 30 분에 걸쳐 부분적으로 첨가한다. 얼음 바스를 사용하여 온도를 35℃ 아래로 유지한다. 혼합물 실온에서 2 시간 동안 교반한다. 혼합물을 물 (400 mL), 포화 수성 바이카르보네이트 (100 mL) 및 TBME (300 mL) 사이에서 분할시킨다. 수성상을 TBME (200 mL) 로 1 회 이상 추출하고 유기상을 물/염수 (약 5:1) 및 염수로 2 회 세척하고, MgSO4 로 건조시킨다. TBME 를 Rotavap 상에서 20℃ 에서 증발시킨다. 미정제 중간체를 SiO2 (3/4 충전된 150 mL 카트리지, DCM/TBME 10:1) 로 여과에 의해 정제한다. 중간체를 다음 단계에서 즉시 사용한다.Intermediate 1 (10000 mg, 26.5 mmol, 1 eq) was dissolved in nitromethane (4 vol.) (40 mL), trimethylsilyl cyanide 98% (10.2 mL, 79.6 mmol, 3 eq) and boron trifluoride dichloride. Ethyl etherate (3.93 mL, 31.8 mmol, 1.2 eq) is added portionwise over 30 minutes. Use an ice bath to maintain the temperature below 35°C. The mixture is stirred at room temperature for 2 hours. Partition the mixture between water (400 mL), saturated aqueous bicarbonate (100 mL), and TBME (300 mL). The aqueous phase is extracted once more with TBME (200 mL) and the organic phase is washed twice with water/brine (about 5:1) and brine and dried over MgSO 4 . TBME is evaporated on Rotavap at 20°C. The crude intermediate is purified by filtration over SiO 2 (150 mL cartridge 3/4 filled, DCM/TBME 10:1). The intermediate is used immediately in the next step.

중간체 3: (2R,3R,4R,5R,6S)-2-(아세톡시메틸)-6-시아노-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-3,5-디일 디아세테이트 Intermediate 3 : (2R,3R,4R,5R,6S)-2-(acetoxymethyl)-6-cyano-4-(4-(3,4,5-trifluorophenyl)-1H-1, 2,3-triazol-1-yl) tetrahydro-2H-pyran-3,5-diyl diacetate

중간체 2 를 DMF (80 mL) 에 용해하고, 5-에티닐-1,2,3-트리플루오로벤젠 (312 mg, 21.2 mmol, 0.8 eq), DIPEA (13.6 mL, 79.6 mmol, 3 eq) 및 CuI (505 mg, 2.65 mmol, 0.1 eq) 를 N2 하에 첨가한다. 황색 혼합물을 실온에서 1 시간 동안 교반한다. 발열성. 황색 용액을 물 (800 mL) 에 천천히 붓고 10 분 동안 교반한다. 베이지색 침전물을 여과해내고 여과물을 폐기한다. 베이지색 고체를 MeOH 로 세척한 다음, EA (300 mL) 에 용해하고 10 분 동안 교반한다. 미세 Cu 잔류물을 여과해내고 여과물을 NH4Cl 용액 (절반 포화) 및 염수로 세척하고, MgSO4 로 건조하고 농축한다. 잔류물을 MeOH (약 100 mL) 로 가루화하고,여과하고 건조시켜 (hv 에서), 원하는 중간체 3a 를 베이지색 고체로서 수득한다.Intermediate 2 was dissolved in DMF (80 mL) and 5-ethynyl-1,2,3-trifluorobenzene (312 mg, 21.2 mmol, 0.8 eq), DIPEA (13.6 mL, 79.6 mmol, 3 eq) and CuI (505 mg, 2.65 mmol, 0.1 eq) is added under N 2 . The yellow mixture is stirred at room temperature for 1 hour. pyrogenic. Pour the yellow solution slowly into water (800 mL) and stir for 10 minutes. Filter off the beige precipitate and discard the filtrate. The beige solid is washed with MeOH, then dissolved in EA (300 mL) and stirred for 10 min. The fine Cu residue is filtered off and the filtrate is washed with NH 4 Cl solution (half saturated) and brine, dried over MgSO 4 and concentrated. The residue is triturated with MeOH (ca. 100 mL), filtered and dried (at hv) to give the desired intermediate 3a as a beige solid.

중간체 3 을 하기 반응식에서 나타낸 바와 같이 추가로 작용화시킨다:Intermediate 3 is further functionalized as shown in the scheme below:

중간체 4: (2R,3R,4S,5R,6R)-3,5-디히드록시-6-(히드록시메틸)-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복시산Intermediate 4: (2R,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H -1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxylic acid

중간체 3 (2800 mg, 5.64 mmol, 1 eq) 을 HCl 25% (20.6 mL, 169 mmol, 30 eq) 에 현탁하고 환류 하 1.5 시간 동안 가열한다. 용액을 수 중에서 MCI® 겔 칼럼 (약 100 mL 겔) 에 적용한다. 칼럼을 중성 pH (5 분획 40 mL) 가 될 때까지 물로 용리한다. 그런 다음, 화합물을 H2O/MeCN (3:1) 으로 용리한다. 40 mL 의 분획을 취한다. 생성물을 함유하는 분획을 먼저 진공 중에서 농축시켜 MeCN 을 제거한 다음, 동결 건조시켜 표제 화합물을 무색 고체로서 수득한다.Intermediate 3 (2800 mg, 5.64 mmol, 1 eq) was suspended in HCl 25% (20.6 mL, 169 mmol, 30 eq) and heated under reflux for 1.5 hours. The solution is applied to an MCI® gel column (approximately 100 mL gel) in water. Elute the column with water until neutral pH (5 fractions, 40 mL). The compound is then eluted with H 2 O/MeCN (3:1). Take aliquots of 40 mL. Fractions containing the product are first concentrated in vacuo to remove MeCN and then freeze-dried to give the title compound as a colorless solid.

중간체 5:Intermediate 5: 메틸 (4aR,6R,7R,8R,8aR)-7-히드록시-2,2-디메틸-8-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)헥사하이드로피라노[3,2-d][1,3]디옥신-6-카르복실레이트Methyl (4aR,6R,7R,8R,8aR)-7-hydroxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3- triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylate

단계 1: 메틸 (2R,3R,4S,5R,6R)-3,5-디히드록시-6-(히드록시메틸)-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복실레이트 Step 1: Methyl (2R,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)- 1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxylate

MeOH (60 ml) 및 THF (40 ml) 중 중간체 4 (14.2 g, 0.036 mol) 의 용액에 MeOH (1.82 ml, 0.00182 mol) 중 1M H2SO4 [H2SO4 95-98% (0.136 ml) 를 2.5 ml MeOH 에 용해시켜 새롭게 제조됨] 를 첨가한다. 혼합물을 실온에서 주말 동안 교반한다. K2CO3 (0.25 g, 0.0018 mol) 을 첨가하고, 혼합물을 여과하고, 용매를 진공 중에서 증발시킨다. 미정제 중간체를 SiO2 (EA/MeOH 9:1) 로 여과에 의해 정제한다. 미정제 생성물 - 무색 고체 - 을 정제 없이 다음 단계에서 사용한다.To a solution of intermediate 4 (14.2 g, 0.036 mol) in MeOH (60 ml) and THF (40 ml) was added 1M H 2 SO 4 [H 2 SO 4 95-98% (0.136 ml) in MeOH (1.82 ml, 0.00182 mol). ) was freshly prepared by dissolving in 2.5 ml MeOH] was added. The mixture is stirred at room temperature over the weekend. K 2 CO 3 (0.25 g, 0.0018 mol) is added, the mixture is filtered and the solvent is evaporated in vacuo. The crude intermediate is purified by filtration over SiO 2 (EA/MeOH 9:1). The crude product - a colorless solid - is used in the next step without purification.

LCMS (A): tR = 0.85 min; [M+H]+ = 403.87LCMS (A): t R = 0.85 min; [M+H] + = 403.87

단계 2: 메틸 (4aR,6R,7R,8R,8aR)-7-히드록시-2,2-디메틸-8-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)헥사히드로피라노[3,2-d][1,3]디옥신-6-카르복실레이트 Step 2 : Methyl (4aR,6R,7R,8R,8aR)-7-hydroxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2 ,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylate

THF (400 ml) 중 단계 1 로부터의 미정제 생성물 (15.5 g, 0.038 mmol) 및 2,2-디메톡시프로판 (7.22 ml, 0.058 mmol) 의 혼합물에 실온에서 PTSA (0.165 g, 0.001 mol) 를 첨가한다. 반응 혼합물을 75℃ 에서 1.5 시간 동안 교반하고, 이 동안 약 150 ml 의 용매를 혼합물에서 증류시킨다. 혼합물을 실온으로 냉각시키고, 수성 포화 NaHCO3 과 EA 사이에서 분할시킨다. 수성 층을 EA 로 1 회 더 추출한다. 조합된 유기 층을 물 및 염수로 세척하고, MgSO4 로 건조하고, 여과하고 진공 중에서 증발시킨다. 미정제 생성물 - 황색 고체 - 를 정제 없이 다음 단계에서 사용한다.To a mixture of the crude product from step 1 (15.5 g, 0.038 mmol) and 2,2-dimethoxypropane (7.22 ml, 0.058 mmol) in THF (400 ml) was added PTSA (0.165 g, 0.001 mol) at room temperature. do. The reaction mixture is stirred at 75° C. for 1.5 hours, during which time about 150 ml of solvent is distilled from the mixture. The mixture is cooled to room temperature and partitioned between aqueous saturated NaHCO 3 and EA. The aqueous layer is extracted once more with EA. The combined organic layers are washed with water and brine, dried over MgSO 4 , filtered and evaporated in vacuo. The crude product - a yellow solid - is used in the next step without purification.

LCMS (A): tR = 0.88 min; [M+H]+ = 444.01LCMS (A): t R = 0.88 min; [M+H] + = 444.01

중간체 6: 메틸 (4aR,6R,7R,8R,8aR)-7-메톡시-2,2-디메틸-8-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)헥사하이드로피라노[3,2-d][1,3]디옥신-6-카르복실레이트Intermediate 6: Methyl (4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2 ,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylate

DMF (180 ml) 중 중간체 5 (16.5 g, 0.037 mol) 의 용액에 0℃ 에서 요오도메탄 (2.57 ml, 0.041 mol) 을 첨가한 후, NaH (미네랄 오일 중 60% 분산액, 1.57 g, 0.041 mol) 를 첨가한다. 혼합물을 실온으로 가온시키고 실온에서 4 시간 동안 교반한다. 혼합물을 0℃ 로 냉각하고, 물을 첨가하여 조심스럽게 켄칭하고, EA 로 2 회 추출한다. 조합된 유기 층을 물 및 염수로 세척하고, MgSO4 로 건조하고, 여과하고 진공 중에서 증발시킨다. 미정제 생성물을 칼럼 크로마토그래피 (6cmx24cm SiO2 칼럼; 구배: 헵탄/EA 2:1 → 헵탄/EA 1:1) 에 의해 정제하여, 원하는 생성물을 황색 고체로서 수득한다.To a solution of intermediate 5 (16.5 g, 0.037 mol) in DMF (180 ml) was added iodomethane (2.57 ml, 0.041 mol) at 0°C, followed by NaH (60% dispersion in mineral oil, 1.57 g, 0.041 mol). ) is added. The mixture is allowed to warm to room temperature and stirred at room temperature for 4 hours. The mixture is cooled to 0° C., carefully quenched by addition of water and extracted twice with EA. The combined organic layers are washed with water and brine, dried over MgSO 4 , filtered and evaporated in vacuo. The crude product is purified by column chromatography (6cmx24cm SiO 2 column; gradient: heptane/EA 2:1 → heptane/EA 1:1) to give the desired product as a yellow solid.

LCMS (A): tR = 0.98 min; [M+H]+ = 458.03LCMS (A): t R = 0.98 min; [M+H] + = 458.03

산 1: (4aR,6R,7R,8R,8aR)-7-메톡시-2,2-디메틸-8-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)헥사하이드로피라노[3,2-d][1,3]디옥신-6-카르복시산Acid 1: (4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2, 3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxine-6-carboxylic acid

THF/MeOH/H2O (3:2:1, 90 ml) 중 중간체 6 (12.8 g, 0.028 mol) 및 LiOH.H2O (1.77 g, 0.042 mmol) 의 혼합물을 실온에서 2 시간 동안 교반한다. 혼합물을 물 (100 ml) 에 의해 희석하고, THF/MeOH 를 증발시킨다. 추가적인 물 (100 ml) 및 시트르산 (물 중 10%) 을 첨가하여 pH 3 에 도달하게 한다. 현탁액을 여과하고, 고체를 물로 세척하고, 미정제 생성물 - 무색 고체 - 를 hv 하에 건조시킨다.A mixture of intermediate 6 (12.8 g, 0.028 mol) and LiOH.H 2 O (1.77 g, 0.042 mmol) in THF/MeOH/H 2 O (3:2:1, 90 ml) is stirred at room temperature for 2 hours. . The mixture is diluted with water (100 ml) and the THF/MeOH is evaporated. Additional water (100 ml) and citric acid (10% in water) are added to reach pH 3. The suspension is filtered, the solid is washed with water and the crude product - a colorless solid - is dried under hv.

LCMS (A): tR = 0.87 min; [M+H]+ = 444.03LCMS (A): t R = 0.87 min; [M+H] + = 444.03

산 2-6 을, 중간체 2 의 부가환화를 위한 상응하는 아세틸렌을 사용하여 산 1 과 유사하게 합성한다.Acids 2-6 are synthesized analogously to acid 1 using the corresponding acetylene for the cycloaddition of intermediate 2.

구조 2 의 중간체의 제조Preparation of intermediates of structure 2

중간체 7: 4-((3-클로로페닐)아미노)테트라히드로푸란-3-올Intermediate 7: 4-((3-chlorophenyl)amino)tetrahydrofuran-3-ol

단계 1: 톨루엔 (4 ml) 중 3,6-디옥사바이시클로[3.1.0]헥산 (400 mg, 4.55 mmol) 및 3-클로로아닐린 (639 mg, 5.01 mmol) 의 용액에 InCl3 (71 mg, 0.32 mmol) 을 첨가하고, 반응 혼합물을 85°에서 3 일 동안 교반한다. 물 및 EA 을 rt 에서 첨가하고, 혼합물을 30 min 동안 rt 에서 교반한다. 수상을 분리하고 EA 로 추출한다. 조합된 org. 층을 MgSO4 로 건조하고, 여과하고, 진공에서 증발시킨다. 조생성물을 prep. LC-MS MS (II) 에 의해 정제하여 표제 중간체 7 을 황색 오일로서 얻는다.Step 1: To a solution of 3,6-dioxabicyclo[3.1.0]hexane (400 mg, 4.55 mmol) and 3-chloroaniline (639 mg, 5.01 mmol) in toluene (4 ml) was added InCl 3 (71 mg , 0.32 mmol) was added and the reaction mixture was stirred at 85° for 3 days. Water and EA are added at rt and the mixture is stirred at rt for 30 min. Separate the aqueous phase and extract with EA. combined org. The layer is dried over MgSO 4 , filtered and evaporated in vacuo. Prepare the crude product. Purification by LC-MS MS (II) gives the title intermediate 7 as a yellow oil.

LCMS (A): tR = 0.72 min; [M+H]+ = 214.06LCMS (A): t R = 0.72 min; [M+H] + = 214.06

아민 1: 4-((tert-부틸디메틸실릴)옥시)-N-(3-클로로페닐)테트라히드로푸란-3-아민Amine 1: 4-((tert-butyldimethylsilyl)oxy)-N-(3-chlorophenyl)tetrahydrofuran-3-amine

단계 2: DCM (10 ml) 중 중간체 7 (250 mg, 1.41 mmol) 및 2,6-루티딘 (333 mg, 3.1 mmol) 의 용액에 0℃ 에서 tert-부틸디메틸실릴 트리플루오로메탄설포네이트 (447 mg, 1.69 mmol) 를 첨가하고, 혼합물을 0℃ 에서 1 h 동안 교반한다. 물을 첨가하고, 혼합물을 sat. aq. NH4Cl 용액으로 켄칭하고, DCM 으로 2 회 추출한다. org. 층을 브라인으로 세척한다. 조합된 org. 층을 MgSO4 로 건조하고, 여과하고, 농축한다. 조생성물을 FC CombiFlash (24 g RediSep 칼럼, 10 min 내 헵탄 중 0-30% EA) 에 의해 정제하여 아민 1 을 무색 오일로서 얻는다. LCMS (A): tR = 1.21 min; [M+H]+ = 328.05Step 2: To a solution of intermediate 7 (250 mg, 1.41 mmol) and 2,6-lutidine (333 mg, 3.1 mmol) in DCM (10 ml) was added tert-butyldimethylsilyl trifluoromethanesulfonate (447 mg, 1.69 mmol) is added and the mixture is stirred at 0° C. for 1 h. Add water and saturate the mixture. aq. Quench with NH 4 Cl solution and extract twice with DCM. org. The layer is washed with brine. combined org. The layer is dried over MgSO 4 , filtered and concentrated. The crude product is purified by FC CombiFlash (24 g RediSep column, 0-30% EA in heptane in 10 min) to give Amine 1 as a colorless oil. LCMS (A): t R = 1.21 min; [M+H] + = 328.05

하기 아민 2 - 11 을 아민 1 과 유사하게 2 단계로 상응하는 아닐린과 3,6-디옥사바이시클로[3.1.0]헥산의 커플링에 의해 제조한다.The following amines 2 - 11 are prepared analogously to amine 1 by coupling the corresponding aniline with 3,6-dioxabicyclo[3.1.0]hexane in two steps.

하기 아민 12 및 13 을 아민 1 과 유사하게 2 단계로 상응하는 아닐린과 tert-부틸 6-옥사-3-아자바이시클로[3.1.0]헥산-3-카르복실레이트의 커플링에 의해 제조한다. 거울상이성질체를 키랄 크로마토그래피에 의해 분리하고, 그 후 실릴화하고, 아미드 커플링에 사용한다.The following amines 12 and 13 are prepared analogously to amine 1 by coupling the corresponding aniline with tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate in two steps. The enantiomers are separated by chiral chromatography, then silylated and used for amide coupling.

* 는 tert-부틸디메틸실릴 (3S,4S)-3-((tert-부틸디메틸실릴)옥시)-4-((3,5-디클로로페닐)아미노)피롤리딘-1-카르복실레이트를 TBSCl 에 의한 히드록시 기의 보호의 부산물로서 함유할 수 있다 * is tert-butyldimethylsilyl (3S,4S)-3-((tert-butyldimethylsilyl)oxy)-4-((3,5-dichlorophenyl)amino)pyrrolidine-1-carboxylate in TBSCl It may contain as a by-product of the protection of the hydroxy group by

하기 아민 14 - 17 을 아민 1 과 유사하게 2 단계로 상응하는 아닐린과 1-(6-옥사-3-아자바이시클로[3.1.0]헥산-3-일)에탄-1-온의 커플링에 의해 제조한다. 16 의 거울상이성질체를 키랄 크로마토그래피에 의해 분리하고, 그 후 실릴화하고, 아미드 커플링에 사용하고, 아민 14, 15 및 17 을 라세미체로서 아미드 커플링에 사용한다.The following amines 14 - 17 were coupled to the corresponding aniline and 1-(6-oxa-3-azabicyclo[3.1.0]hexan-3-yl)ethan-1-one in two steps, similarly to amine 1. manufactured by The enantiomers of 16 were separated by chiral chromatography, then silylated and used for amide coupling, and amines 14, 15 and 17 were racemates and used for amide coupling.

하기 아민 18 - 21 을 아민 1 과 유사하게 2 단계로 상응하는 아닐린과 3,7-디옥사바이시클로[4.1.0]헵탄의 커플링에 의해 제조한다. 이들 경우에, 얻어진 아미노알코올을 키랄 크로마토그래피에 의해 분리하고, 그 후 실릴화하고, 아미드 커플링에 사용한다.The following amines 18 - 21 are prepared analogously to amine 1 by coupling the corresponding aniline with 3,7-dioxabicyclo[4.1.0]heptane in two steps. In these cases, the obtained aminoalcohol is separated by chiral chromatography, then silylated, and used for amide coupling.

하기 아민 22 - 25 을 아민 1 과 유사하게 2 단계로 상응하는 아닐린과 tert-부틸 7-옥사-3-아자바이시클로[4.1.0]헵탄-3-카르복실레이트의 커플링에 의해 제조한다. 이들 경우에, 얻어진 아미노알코올을 키랄 크로마토그래피에 의해 분리하고, 그 후 실릴화하고, 아미드 커플링에 사용한다.The following amines 22 - 25 are prepared analogously to amine 1 by coupling the corresponding aniline with tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate in two steps. In these cases, the obtained aminoalcohol is separated by chiral chromatography, then silylated, and used for amide coupling.

B - 실시예의 제조B - Preparation of Examples

실시예 1: (2R,3R,4S,5R,6R)-N-(3-클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드Example 1: (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide

단계 1: (4aR,6R,7R,8R,8aR)-N-((3S,4R)-4-((tert-부틸디메틸실릴)옥시)테트라히드로푸란-3-일)-N-(3-클로로페닐)-7-메톡시-2,2-디메틸-8-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)헥사하이드로피라노[3,2-d][1,3]디옥신-6-카르복사미드 Step 1: (4aR,6R,7R,8R,8aR)-N-((3S,4R)-4-((tert-butyldimethylsilyl)oxy)tetrahydrofuran-3-yl)-N-(3- Chlorophenyl)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydro Pyrano[3,2-d][1,3]dioxin-6-carboxamide

DCM (4 mL) 중 산 1 (50 mg; 0.113 mmol) 및 아민 1 (39mg, 0.118 mmol) 의 혼합물에 rt 에서 인(V) 산염화물 (피리딘 중 1M 용액, 0.14 mL, 0.135 mmol) 을 첨가하고, 혼합물을 rt 에서 24h 동안 교반한다. 물을 첨가하고, 혼합물을 sat. aq. NH4Cl 용액으로 켄칭하고, DCM 으로 2 회 추출한다. org. 층을 브라인으로 세척한다. 조합된 org. 층을 MgSO4 로 건조하고, 여과하고, 농축한다. 조생성물을 prep. LC-MS (I) 에 의해 정제하여 중간체 8 (부분입체이성질체의 혼합물로서) 을 얻는다.To a mixture of acid 1 (50 mg; 0.113 mmol) and amine 1 (39 mg, 0.118 mmol) in DCM (4 mL) was added phosphorus(V) acid chloride (1M solution in pyridine, 0.14 mL, 0.135 mmol) at rt; The mixture is stirred at rt for 24 h. Add water and saturate the mixture. aq. Quench with NH 4 Cl solution and extract twice with DCM. org. The layer is washed with brine. combined org. The layer is dried over MgSO 4 , filtered and concentrated. Prepare the crude product. Purification by LC-MS (I) gives intermediate 8 (as a mixture of diastereomers).

LCMS (A): tR = 1.29/1.30 min; [M+H]+ = 753.10LCMS (A): t R = 1.29/1.30 min; [M+H] + = 753.10

단계 2: (2R,3R,4S,5R,6R)-N-(3-클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드 Step 2: (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxy tetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro- 2H-pyran-2-carboxamide

디옥산 (1 ml) 및 물 (0.5 ml) 중 중간체 8 (부분입체이성질체의 혼합물) (74 mg, 0.98 mmol) 의 용액에 0℃ 에서 TFA (0.60 ml, 7.8 mmol) 을 첨가하고, 반응 혼합물을 rt 에서 21 h 동안 교반한다. 용매를 증발시키고, MeCN 을 첨가하고, 혼합물을 25% aq. NH4OH 용액으로 염기성화하고 (pH 11 까지), 생성물을 prep. LCMS (II) 에 의해 정제하여 최종 화합물을 부분입체이성질체의 혼합물로서 얻고, 이것을 키랄 칼럼 크로마토그래피에 의해 분리하여 실시예 1 및 실시예 30 을 얻는다.To a solution of intermediate 8 (mixture of diastereomers) (74 mg, 0.98 mmol) in dioxane (1 ml) and water (0.5 ml) was added TFA (0.60 ml, 7.8 mmol) at 0° C. and the reaction mixture was Stir at rt for 21 h. The solvent was evaporated, MeCN was added and the mixture was concentrated to 25% aq. After basification with NH 4 OH solution (to pH 11), the product was prepared. Purification by LCMS (II) gives the final compound as a mixture of diastereomers, which is separated by chiral column chromatography to obtain Examples 1 and 30.

실시예 59: (2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드Example 59: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4 -Hydroxypyrrolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) Tetrahydro-2H-pyran-2-carboxamide

단계 1: tert-부틸 (3S,4S)-3-((tert-부틸디메틸실릴)옥시)-4-((4aR,6R,7R,8R,8aR)-N-(3,5-디클로로페닐)-7-메톡시-2,2-디메틸-8-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)헥사하이드로피라노[3,2-d][1,3]디옥신-6-카르복사미도)피롤리딘-1-카르복실레이트 Step 1: tert-Butyl (3S,4S)-3-((tert-butyldimethylsilyl)oxy)-4-((4aR,6R,7R,8R,8aR)-N-(3,5-dichlorophenyl) -7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[ 3,2-d][1,3]dioxine-6-carboxamido)pyrrolidine-1-carboxylate

DCM (35 mL) 중 산 1 (450 mg; 1.01 mmol) 및 아민 12 (554 mg, 1.07 mmol) 의 혼합물에 rt 에서 인(V) 산염화물 (피리딘 중 1M 용액, 1.22 mL, 1.22 mmol) 을 첨가하고, 혼합물을 rt 에서 24h 동안 교반한다. 물을 첨가하고, 혼합물을 sat. aq. NH4Cl 용액으로 켄칭하고, DCM 으로 2 회 추출한다. org. 층을 브라인으로 세척한다. 조합된 org. 층을 MgSO4 로 건조하고, 여과하고, 농축한다. 조생성물을 ISCO (24 g RediSep 칼럼, 15 min 내 헵탄 중 0-80% EA) 에 의해 정제하여 중간체 9 를 황색 포움 (foam) 으로서 얻는다.To a mixture of acid 1 (450 mg; 1.01 mmol) and amine 12 (554 mg, 1.07 mmol) in DCM (35 mL) was added phosphorus(V) acid chloride (1M solution in pyridine, 1.22 mL, 1.22 mmol) at rt. , the mixture is stirred at rt for 24 h. Add water and saturate the mixture. aq. Quench with NH 4 Cl solution and extract twice with DCM. org. The layer is washed with brine. combined org. The layer is dried over MgSO 4 , filtered and concentrated. The crude product is purified by ISCO (24 g RediSep column, 0-80% EA in heptane in 15 min) to give intermediate 9 as a yellow foam.

LCMS (A): tR = 1.37 min; [M+H]+ = 886.09LCMS (A): t R = 1.37 min; [M+H] + = 886.09

생성물은 tert-부틸디메틸실릴 (3S,4S)-3-((tert-부틸디메틸실릴)옥시)-4-((4aR,6R,7R,8R,8aR)-N-(3,5-디클로로페닐)-7-메톡시-2,2-디메틸-8-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)헥사하이드로피라노[3,2-d][1,3]디옥신-6-카르복사미도)피롤리딘-1-카르복실레이트를 함유할 수 있다.The product is tert-butyldimethylsilyl (3S,4S)-3-((tert-butyldimethylsilyl)oxy)-4-((4aR,6R,7R,8R,8aR)-N-(3,5-dichlorophenyl )-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano [3,2-d][1,3]dioxine-6-carboxamido)pyrrolidine-1-carboxylate.

LCMS (A): tR = 1.42 min; [M+H]+ = 944.10LCMS (A): t R = 1.42 min; [M+H] + = 944.10

단계 2: (2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드 Step 2: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4- Hydroxypyrrolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra Hydro-2H-pyran-2-carboxamide

디옥산 (10 ml) 및 물 (5 ml) 중 중간체 9 (486 mg, 0.51 mmol) 의 용액에 0℃ 에서 TFA (1.97 ml, 25.7 mmol) 을 첨가하고, 반응 혼합물을 rt 에서 2 주 동안 교반한다 [3 일 및 1 주 후에 추가의 TFA (0.5 ml) 를 첨가한다]. EA 을 첨가하고, 혼합물을 25% aq. NH4OH 용액으로 염기성화하고 (pH 9 까지), EA 로 2 회 추출한다. org. 층을 브라인으로 세척한다. 조합된 org. 층을 MgSO4 로 건조하고, 여과하고, 농축한다. 조생성물을 ISCO (12 g RediSep 칼럼, DCM 중 0-30% 7N NH3/MeOH) 및 prep. LC-MS (II) 에 의해 정제하여 최종 생성물을 무색 고체로서 얻는다.To a solution of intermediate 9 (486 mg, 0.51 mmol) in dioxane (10 ml) and water (5 ml) is added TFA (1.97 ml, 25.7 mmol) at 0° C. and the reaction mixture is stirred at rt for 2 weeks. [Additional TFA (0.5 ml) is added after 3 days and 1 week]. EA was added and the mixture was dissolved in 25% aq. Basify with NH 4 OH solution (to pH 9) and extract twice with EA. org. The layer is washed with brine. combined org. The layer is dried over MgSO 4 , filtered and concentrated. The crude product was purified by ISCO (12 g RediSep column, 0-30% 7N NH 3 /MeOH in DCM) and prep. Purification by LC-MS (II) gives the final product as a colorless solid.

실시예 72: (2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드.Example 72: (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo- 5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-tria Zol-1-yl)tetrahydro-2H-pyran-2-carboxamide.

이 생성물을 2 단계로 실시예 1 과 유사하게 산 1 및 아민 15 로부터 제조한다. 부분입체이성질체를 키랄 크로마토그래피에 의해 분리하여 실시예 72 및 79 를 얻는다.This product is prepared analogously to Example 1 from acid 1 and amine 15 in two steps. The diastereomers are separated by chiral chromatography to give Examples 72 and 79.

N-아세틸 유사체를 또한 2 단계 절차 - 상응하는 NH 생성물로부터 퍼아세틸화 및 O-탈아세틸화로 실시예 71 에 제시된 바와 같이 제조할 수 있다.N-acetyl analogs can also be prepared as shown in Example 71 in a two-step procedure - peracetylation and O-deacetylation from the corresponding NH products.

실시예 71:Example 71: (2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-5 -Hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) Tetrahydro-2H-pyran-2-carboxamide

단계 1: (2R,3R,4R,5R,6R)-6-(((3S,4S)-4-아세톡시-1-아세틸피롤리딘-3-일)(3,5-디클로로페닐)카르바모일)-2-(아세톡시메틸)-5-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-3-일 아세테이트 Step 1: (2R,3R,4R,5R,6R)-6-(((3S,4S)-4-acetoxy-1-acetylpyrrolidin-3-yl)(3,5-dichlorophenyl)carboxylic vamoyl)-2-(acetoxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) Tetrahydro-2H-pyran-3-yl acetate

DCM (1.5 ml) 중 화합물 59 (23 mg, 0.0364 mmol) 의 용액에 rt 에서 트리에틸아민 (0.050 ml, 0.364 mmol), 무수 아세트산 (0.017 ml, 0.182 mmol) 및 DMAP (6.7 mg, 0.054 mmol) 을 첨가하고, 혼합물을 rt 에서 15 min 동안 교반한다. 혼합물을 sat. aq. NH4Cl 용액으로 켄칭하고, DCM 으로 2 회 추출한다. org. 층을 브라인으로 세척한다. 조합된 org. 층을 MgSO4 로 건조하고, 여과하고, 농축한다. 중간체 11 을 정제하지 않고 다음 단계에 사용한다.To a solution of compound 59 (23 mg, 0.0364 mmol) in DCM (1.5 ml) was added triethylamine (0.050 ml, 0.364 mmol), acetic anhydride (0.017 ml, 0.182 mmol) and DMAP (6.7 mg, 0.054 mmol) at rt. Add and stir the mixture at rt for 15 min. saturate the mixture. aq. Quench with NH 4 Cl solution and extract twice with DCM. org. The layer is washed with brine. combined org. The layer is dried over MgSO 4 , filtered and concentrated. Intermediate 11 is used in the next step without purification.

LCMS (A): tR = 1.07 min; [M+H]+ = 800.03LCMS (A): t R = 1.07 min; [M+H] + = 800.03

단계 2: (2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드 Step 2: (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl )-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1 -1) Tetrahydro-2H-pyran-2-carboxamide

MeOH (1.5 ml) 중 중간체 11 (27 mg, 0.0337 mmol) 의 용액에 rt 에서 MeOH 중 NaOMe 의 용액 (1.26 ml; 0.25 mg NaOMe 을 1 ml MeOH 에 용해시켜 자체 제조함) 을 첨가하고, 혼합물을 3h 동안 교반한다. 혼합물을 sat. aq. NH4Cl 용액으로 켄칭하고, 에틸 아세테이트로 2 회 추출한다. org. 층을 브라인으로 세척한다. 조합된 org. 층을 MgSO4 로 건조하고, 여과하고, 농축한다. 조생성물을 prep. LC-MS (II) 에 의해 정제하여 최종 생성물을 무색 고체로서 얻는다.To a solution of intermediate 11 (27 mg, 0.0337 mmol) in MeOH (1.5 ml) was added a solution of NaOMe in MeOH (1.26 ml; prepared in-house by dissolving 0.25 mg NaOMe in 1 ml MeOH) at rt and the mixture was incubated for 3 h. Stir for a while. saturate the mixture. aq. Quench with NH 4 Cl solution and extract twice with ethyl acetate. org. The layer is washed with brine. combined org. The layer is dried over MgSO 4 , filtered and concentrated. Prepare the crude product. Purification by LC-MS (II) gives the final product as a colorless solid.

LCMS (A): tR = 0.85 min; [M+H]+ = 673.86.LCMS (A): t R = 0.85 min; [M+H] + = 673.86.

실시예 90: (2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-N-((3S,4S)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드Example 90: (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine -3-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3- triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide

에틸 포르메이트 (0.44 ml, 5.33 mmol) 중 실시예 61 (35 mg, 0.053 mmol) 의 용액에 트리에틸아민 (0.008 ml, 0.053 mmol) 을 첨가하고, 반응 혼합물을 밀봉된 튜브 내에서 50℃ 에서 4h 동안 교반한다. 용매를 증발시키고, 혼합물을 prep. LC-MS (II) 에 의해 정제하여 최종 생성물을 무색 고체로서 얻는다.To a solution of Example 61 (35 mg, 0.053 mmol) in ethyl formate (0.44 ml, 5.33 mmol) was added triethylamine (0.008 ml, 0.053 mmol) and the reaction mixture was incubated in a sealed tube at 50° C. for 4 h. Stir for a while. Evaporate the solvent and prepare the mixture. Purification by LC-MS (II) gives the final product as a colorless solid.

실시예 99: (2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드Example 99: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-3 -Hydroxytetrahydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1 -1) Tetrahydro-2H-pyran-2-carboxamide

이 생성물을 2 단계로 실시예 1 과 유사하게 산 1 및 아민 18 로부터 제조한다.This product is prepared analogously to Example 1 from acid 1 and amine 18 in two steps.

실시예 105: (2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시테트라히드로-2H-피란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드Example 105: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4 -Hydroxytetrahydro-2H-pyran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1 -1) Tetrahydro-2H-pyran-2-carboxamide

이 생성물을 2 단계로 실시예 1 과 유사하게 산 1 및 아민 20 로부터 제조한다.This product is prepared analogously to Example 1 from acid 1 and amine 20 in two steps.

실시예 109: (2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-3-히드록시피페리딘-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드Example 109: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-3 -Hydroxypiperidin-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) Tetrahydro-2H-pyran-2-carboxamide

이 생성물을 2 단계로 실시예 1 과 유사하게 산 1 및 아민 22 로부터 제조한다.This product is prepared analogously to Example 1 from acid 1 and amine 22 in two steps.

실시예 113: (2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피페리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드Example 113: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4 -Hydroxypiperidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) Tetrahydro-2H-pyran-2-carboxamide

이 생성물을 2 단계로 실시예 1 과 유사하게 산 1 및 아민 24 로부터 제조한다.This product is prepared analogously to Example 1 from acid 1 and amine 24 in two steps.

하기 화합물을 실시예 1 과 유사하게 상응하는 산 및 아민으로부터, 또는 언급된 실시예 59, 71, 72, 90, 99, 105, 109, 또는 113 에 관해 기재된 바와 같이 제조한다.The following compounds are prepared analogously to Example 1 from the corresponding acids and amines or as described in relation to the mentioned Examples 59, 71, 72, 90, 99, 105, 109, or 113.

표 1:Table 1:

II. 생물학적 어세이II. biological assay

화합물 저해 활성의 평가 (ICEvaluation of compound inhibitory activity (IC 5050 ))

화합물의 저해 활성을 경쟁적 결합 어세이에서 결정한다. 이러한 분광광도 어세이로, 마이크로플레이트-흡착된 당단백질, 아시알로페투인 (ASF) 에 대한 비오티닐화된 인간 Gal-3 (hGal-3) 또는 인간 Gal-1 (hGal-1) 각각의 결합을 측정한다 (Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5052-7.). 대안적으로, 그리고 바람직하게는, 6 개 시스테인 모두가 세린에 의해 치환되는 인간 Gal-1 버전이 사용될 수 있다.The inhibitory activity of the compounds is determined in competitive binding assays. This spectrophotometric assay assays binding of biotinylated human Gal-3 (hGal-3) or human Gal-1 (hGal-1), respectively, to the microplate-adsorbed glycoprotein, asialofetuin (ASF). (Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5052-7.). Alternatively, and preferably, the human Gal-1 version can be used in which all six cysteines are replaced by serine.

간략하게, 화합물을 DMSO 에서 연속 희석한다 (작업 희석물). ASF-코팅된 384 웰 플레이트에, 1.2 μL 의 화합물 작업 희석물을 첨가하고 혼합한 어세이 완충제 중 22.8 μL/웰의 비오티닐화된 hGal-3 또는 hGal-1 (즉, 300-1000 ng/mL 비오티닐화된 hGal-3 또는 hGal-1) 을 보충한다. Briefly, compounds are serially diluted in DMSO (working dilutions). To an ASF-coated 384 well plate, 1.2 μL of compound working dilutions were added and mixed at 22.8 μL/well of biotinylated hGal-3 or hGal-1 (i.e., 300-1000 ng/mL) in assay buffer. Supplement with biotinylated hGal-3 or hGal-1).

플레이트를 3 시간 동안 4℃ 에서 인큐베이션한 다음, 냉각 어세이 완충제 (3x50uL) 로 세척하고, 1 시간 동안 25 μL/웰의 스트렙타비딘-퍼옥시다아제 용액 (어세이 완충제 중 80 ng/mL 로 희석) 과 함께 4℃ 에서 인큐베이션한 후, 어세이 완충제 (3x50uL) 로 추가 세척 단계를 시행한다. 마지막으로, 25 μL/웰의 ABTS 기질을 첨가한다. 30 내지 45 분 후 OD (410nm) 를 기록하고, IC50 값을 계산한다.Plates were incubated at 4°C for 3 hours, then washed with cold assay buffer (3x50uL) and 25 μL/well of streptavidin-peroxidase solution (diluted to 80 ng/mL in assay buffer) for 1 hour. After incubation at 4°C, an additional washing step is performed with assay buffer (3x50uL). Finally, add 25 μL/well of ABTS substrate. After 30 to 45 minutes the OD (410 nm) is recorded and the IC 50 value is calculated.

계산된 IC50 값은 일일 어세이 성능에 따라 변동될 수 있다. 이러한 유형의 변동은 당업자에게 알려져 있다. 여러 측정값으로부터의 IC50 값을 평균 값으로서 제시한다.Calculated IC 50 values may vary depending on daily assay performance. This type of variation is known to those skilled in the art. IC 50 values from multiple measurements are presented as average values.

표 2 - hGal-3 에 대한 활성 (ICTable 2 - Activity against hGal-3 (IC 5050 , nM):, nM):

표 3 - hGal-1 에 대한 활성 (ICTable 3 - Activity against hGal-1 (IC 5050 , nM):, nM):

본 발명의 화합물은 당해 기술분야에 잘 알려진 통상적인 분석법을 사용하여 일반적인 약동학 및 약리학적 특성에 관하여; 예를 들어 용해도, 투과성, 대사 안정성, 흡수 등과 같은 측면을 포함하는 상이한 종 (예컨대 랫트 또는 개) 에서의 생체이용률과 관련하여; 또는 예를 들어 당해 기술분야에 잘 알려진 통상적인 분석법을 사용하여 약물 안전성에 관한 특성 및/또는 독성 특성에 관하여, 예를 들어 시토크롬 P450 효소 저해 및 시간 의존적 저해, 프레그난 X 수용체 (PXR) 활성화, 글루타티온 결합 또는 광독성 거동과 관련하여 추가로 특성화될 수 있다.The compounds of the present invention are evaluated for their general pharmacokinetic and pharmacological properties using conventional analytical methods well known in the art; With regard to bioavailability in different species (such as rat or dog), including for example aspects such as solubility, permeability, metabolic stability, absorption, etc.; or with regard to drug safety properties and/or toxicity properties, for example by using conventional assays well known in the art, such as cytochrome P450 enzyme inhibition and time-dependent inhibition, pregnane It can be further characterized with respect to glutathione binding or phototoxic behavior.

Claims (14)

식 (I) 의 화합물:

식에서
n 및 m 은 각각, 독립적으로, 정수 1 또는 2 를 나타내며, n+m 은 2 또는 3 이고;
X 는 O 또는 NR 2 를 나타내며; 여기에서 R 2 는 수소, C1-3-알킬, -CO-H, -SO2-C1-3-알킬, 또는 -CO-C1-3-알킬을 나타내고;
Ar 1 은 하기를 나타내고
· 아릴, 이는 일-, 이-, 삼-, 사-, 또는 오-치환되며, 여기에서 치환기는 독립적으로 할로겐; 메틸; 시아노; 메톡시; 트리플루오로메틸; 트리플루오로메톡시; 및 NR N11 R N12 로부터 선택되며, 여기에서 R N11 은 수소를 나타내고 R N12 는 히드록시-C2-3-알킬을 나타내거나, 또는 R N11 및 R N12 는 그들이 부착되어 있는 질소 원자와 함께 모르폴린-4-일, 아제티딘-1-일, 피롤리딘-1-일, 및 피페리딘-1-일로부터 선택되는 4- 내지 6-원 헤테로시클릴을 형성하며, 상기 4- 내지 6-원 헤테로시클릴은 미치환 또는 히드록시로 일-치환됨;
· 5- 또는 6-원 헤테로아릴, 상기 5- 또는 6-원 헤테로아릴은 독립적으로 미치환, 일- 또는 이-치환되며, 여기에서 치환기는 독립적으로 할로겐, 메틸, 시아노, 및 메톡시로부터 선택됨; 또는
· 9- 또는 10-원 헤테로아릴, 상기 9- 또는 10-원 헤테로아릴은 독립적으로 미치환, 또는 메틸로 일-치환됨;
R 1 은 하기를 나타내고
· 히드록시;
· C1-3-알콕시;
· -O-CO-C1-3-알킬;
· -O-CH2-CH2-OH; 또는
· -O-CH2-CO-R 1X , 여기에서 R 1X 는 하기를 나타냄
≫ -히드록시;
≫ 모르폴린-4-일; 또는
≫ -NR N21 R N22 , 여기에서 R N21 및 R N22 는 그들이 부착되어 있는 질소 원자와 함께 아제티딘-1-일, 피롤리딘-1-일, 및 피페리딘-1-일로부터 선택되는 4- 내지 6-원 헤테로시클릴을 형성하며, 상기 4- 내지 6-원 헤테로시클릴은 히드록시로 일-치환됨;
L 은 직접 결합, 메틸렌, 또는 에틸렌을 나타내고; 및
Ar 2 는 하기를 나타냄
· 페닐 또는 5- 또는 6-원 헤테로아릴, 상기 페닐 또는 5- 또는 6-원 헤테로아릴은 독립적으로 미치환, 또는 일-, 이- 또는 삼-치환되며; 여기에서 치환기는 독립적으로 C1-6-알킬, C3-6-시클로알킬, -CH2-C3-6-시클로알킬, C1-3-플루오로알킬, C1-3-플루오로알콕시, C1-3-알콕시, 할로겐, 모르폴린-4-일, 아미노, 에티닐, 및 시아노로부터 선택됨;
· 9-원 바이시클릭 헤테로아릴 또는 10-원 바이시클릭 헤테로아릴, 상기 9- 또는 10-원 바이시클릭 헤테로아릴은 독립적으로 미치환, 일- 또는 이-치환되며, 여기에서 치환기는 독립적으로 메틸, 메톡시, 및 할로겐으로부터 선택됨; 또는
· 나프틸;
또는 이의 약학적으로 허용가능한 염.Compounds of formula (I):

In Eq.
n and m each independently represent the integer 1 or 2, and n+m is 2 or 3;
X represents O or N R 2 ; where R 2 represents hydrogen, C 1-3 -alkyl, -CO-H, -SO 2 -C 1-3 -alkyl, or -CO-C 1-3 -alkyl;
Ar 1 represents the following
· Aryl, which is mono-, di-, tri-, tetra-, or penta-substituted, wherein the substituents are independently halogen; methyl; cyano; methoxy; trifluoromethyl; trifluoromethoxy; and NR N11 R N12 , wherein R N11 represents hydrogen and R N12 represents hydroxy-C 2-3 -alkyl, or R N11 and R N12 together with the nitrogen atom to which they are attached are Forming a 4- to 6-membered heterocyclyl selected from polin-4-yl, azetidin-1-yl, pyrrolidin-1-yl, and piperidin-1-yl, wherein the 4- to 6-membered heterocyclyl is selected from -the original heterocyclyl is unsubstituted or mono-substituted with hydroxy;
5- or 6-membered heteroaryl, wherein the 5- or 6-membered heteroaryl is independently unsubstituted, mono- or di-substituted, wherein the substituents are independently selected from halogen, methyl, cyano, and methoxy. selected; or
· 9- or 10-membered heteroaryl, wherein the 9- or 10-membered heteroaryl is independently unsubstituted or mono-substituted with methyl;
R 1 represents the following
· Hydroxy;
· C 1-3 -alkoxy;
· -O-CO-C 1-3 -alkyl;
· -O-CH 2 -CH 2 -OH; or
-O-CH 2 -CO- R 1X , where R 1X represents
≫ -Hydroxy;
≫ Morpholin-4-yl; or
≫ -N R N21 R N22 , wherein R N21 and R N22 together with the nitrogen atom to which they are attached are selected from azetidin-1-yl, pyrrolidin-1-yl, and piperidin-1-yl. forming a 4- to 6-membered heterocyclyl, wherein the 4- to 6-membered heterocyclyl is mono-substituted with hydroxy;
L represents a direct bond, methylene, or ethylene; and
Ar 2 represents
· phenyl or 5- or 6-membered heteroaryl, wherein said phenyl or 5- or 6-membered heteroaryl is independently unsubstituted, or mono-, di- or tri-substituted; Here, the substituents are independently C 1-6 -alkyl, C 3-6 -cycloalkyl, -CH 2 -C 3-6 -cycloalkyl, C 1-3 -fluoroalkyl, C 1-3 -fluoroalkoxy , C 1-3 -alkoxy, halogen, morpholin-4-yl, amino, ethynyl, and cyano;
· 9-membered bicyclic heteroaryl or 10-membered bicyclic heteroaryl, wherein the 9- or 10-membered bicyclic heteroaryl is independently unsubstituted, mono- or di-substituted, wherein the substituents are independently selected from methyl, methoxy, and halogen; or
· Naphthyl;
Or a pharmaceutically acceptable salt thereof. 제 1 항에 있어서, 상기 화합물이 또한 식 (IS) 의 화합물인 화합물:

또는 이의 약학적으로 허용가능한 염.The compound according to claim 1, wherein said compound is also a compound of formula ( IS ):

Or a pharmaceutically acceptable salt thereof. 제 1 항 또는 제 2 항에 있어서, Ar 1 이 페닐을 나타내며, 이는 이- 또는 삼-치환되며, 여기에서 치환기는 독립적으로 할로겐, 메틸, 및 시아노로부터 선택되며; 상기 치환기 중 적어도 하나는 상기 페닐의 메타- 또는 파라-위치에 부착되어 있는 화합물;
또는 이의 약학적으로 허용가능한 염.3. The method according to claim 1 or 2, wherein Ar 1 represents phenyl, which is di- or tri-substituted, wherein the substituents are independently selected from halogen, methyl, and cyano; Compounds in which at least one of the substituents is attached to the meta- or para-position of the phenyl;
Or a pharmaceutically acceptable salt thereof. 제 1 항 또는 제 2 항에 있어서, Ar 1 이 하기를 나타내는 화합물

또는 이의 약학적으로 허용가능한 염.The compound according to claim 1 or 2, wherein Ar 1 represents

Or a pharmaceutically acceptable salt thereof. 제 1 항 내지 제 4 항 중 어느 한 항에 있어서, R 1 이 메톡시를 나타내는 화합물;
또는 이의 약학적으로 허용가능한 염.The compound according to any one of claims 1 to 4, wherein R 1 represents methoxy;
Or a pharmaceutically acceptable salt thereof. 제 1 항 내지 제 5 항 중 어느 한 항에 있어서, L 이 직접 결합을 나타내는 화합물;
또는 이의 약학적으로 허용가능한 염.The compound according to any one of claims 1 to 5, wherein L represents a direct bond;
Or a pharmaceutically acceptable salt thereof. 제 1 항 내지 제 6 항 중 어느 한 항에 있어서, Ar 2 가 페닐을 나타내며, 이는 일-, 또는 이-치환되며, 여기에서 치환기는 독립적으로 C1-4-알킬, C1-3-알콕시, 할로겐, 및 시아노로부터 선택되는 화합물;
또는 이의 약학적으로 허용가능한 염.The method according to any one of claims 1 to 6, wherein Ar 2 represents phenyl, which is mono-, or di-substituted, wherein the substituents are independently C 1-4 -alkyl, C 1-3 -alkoxy Compounds selected from , halogen, and cyano;
Or a pharmaceutically acceptable salt thereof. 제 1 항 내지 제 5 항 중 어느 한 항에 있어서, 단편 -L-Ar 2 가 하기를 나타내는 화합물:

또는 이의 약학적으로 허용가능한 염.Compound according to any one of claims 1 to 5, wherein the fragment -L - Ar 2 represents:

Or a pharmaceutically acceptable salt thereof. 제 1 항에 있어서, 상기 화합물이 하기와 같은 화합물:
(2R,3R,4S,5R,6R)-N-(3-클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-N-(3-아이오도페닐)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-클로로-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-시아노-5-메톡시페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-시아노-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-시아노-5-플루오로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-N-(3-아이오도페닐)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-클로로-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-시아노-5-메톡시페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-시아노-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-시아노-5-플루오로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디브로모페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-4-히드록시테트라히드로푸란-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피롤리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피롤리딘-3-일)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디브로모페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디브로모페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3-브로모-5-메틸페닐)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-4-(4-(3,5-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-4-(4-(4-클로로-3,5-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디브로모페닐)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-아세틸-4-히드록시피롤리딘-3-일)-N-(3,5-디클로로페닐)-4-(4-(3,4-디클로로페닐)-1H-1,2,3-트리아졸-1-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-N-((3S,4S)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-N-((3S,4S)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-4-(4-(4-브로모-2,3-디플루오로페닐)-1H-1,2,3-트리아졸-1-일)-N-(3,5-디클로로페닐)-N-((3S,4S)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-N-((3S,4S)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-N-((3R,4R)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-N-((3R,4R)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-4-(4-(2,3-디플루오로-4-메틸페닐)-1H-1,2,3-트리아졸-1-일)-N-((3R,4R)-1-포르밀-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-N-((3S,4S)-4-히드록시-1-메틸피롤리딘-3-일)-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-N-((3S,4S)-1-에틸-4-히드록시피롤리딘-3-일)-5-히드록시-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-N-((3S,4S)-4-히드록시-1-(메틸술포닐)피롤리딘-3-일)-6-(히드록시메틸)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-클로로-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4S)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4R)-3-히드록시테트라히드로-2H-피란-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시테트라히드로-2H-피란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시테트라히드로-2H-피란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시테트라히드로-2H-피란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시테트라히드로-2H-피란-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-3-히드록시피페리딘-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-시아노페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-3-히드록시피페리딘-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-3-히드록시피페리딘-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-3-히드록시피페리딘-4-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3,5-디클로로페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피페리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3S,4S)-4-히드록시피페리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드; 또는
(2R,3R,4S,5R,6R)-N-(3-브로모-5-메틸페닐)-5-히드록시-6-(히드록시메틸)-N-((3R,4R)-4-히드록시피페리딘-3-일)-3-메톡시-4-(4-(3,4,5-트리플루오로페닐)-1H-1,2,3-트리아졸-1-일)테트라히드로-2H-피란-2-카르복사미드;
또는 이의 약학적으로 허용가능한 염.2. The compound according to claim 1, wherein said compound is:
(2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran -3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran -2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydro furan-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H- Pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-N-( 3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H- Pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetra hydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4- Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-cyano-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3- triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro- 2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1, 2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3- triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro- 2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1, 2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N- (3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N- (3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1 ,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3- methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2 ,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1- yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2 -Carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole- 1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran -2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-tria Zol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H -pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole- 1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran -2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran -3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran -2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydro furan-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H- Pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-N-( 3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H- Pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetra hydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4- Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-cyano-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydride Roxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4 -Hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3-Bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3- triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro- 2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1, 2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3- triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro- 2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1, 2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N- (3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N- (3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1 ,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3- methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2 ,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1- yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2 -Carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole- 1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran -2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-tria Zol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H -pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole- 1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran -2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxyp rolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4 -Hydroxypyrrolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydride Roxypyrrolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidin-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3- triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidin-3-yl)-3-methoxytetrahydro- 2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidin-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1- yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidin-3-yl)-3-methoxytetrahydro-2H-pyran-2 -Carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxyp rolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4 -Hydroxypyrrolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydride Roxypyrrolidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidin-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidin-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidin-3-yl)-3-methoxytetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-5 -Hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-bromo-2 ,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dibromophenyl) -4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-5 -Hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-cyano Phenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole- 1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-bromo-2 ,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dibromophenyl) -4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3 -methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3-bromo-5-methylphenyl) -4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dibromophenyl) -5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dibromophenyl) -5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-4 -(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-4 -(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-meth Toxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-chloro-3, 5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3- methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-chloro-3, 5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3- methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-chloro-3, 5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-4-(4-(4-chloro-3, 5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-4 -(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H -pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidin-3-yl)-N-(3,5-dichlorophenyl)-4 -(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H -pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine-3 -yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole -1-yl)tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidin-3-yl )-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1 -1) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N -(3,5-dichlorophenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidin-3-yl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidin-3-yl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidine-3 -yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole -1-yl)tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidin-3-yl )-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1 -1) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2, 3-triazol-1-yl)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidin-3-yl)-5-hydroxy-6-(hydroxymethyl)- 3-methoxytetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((3S,4S)-4-hydroxy-1-methylpyrrolidine -3-yl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-N-((3S,4S)-1-ethyl-4-hydroxypyrrolidin-3-yl) -5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((3S,4S)-4-hydroxy-1-(methylsulfonyl ) pyrrolidin-3-yl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-tria zol-1-yl)tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-3-hydroxytetra hydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-3- Hydroxytetrahydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1- 1) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-3 -Hydroxytetrahydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1 -1) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-3-hydride Roxytetrahydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl ) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-3-hydroxytetra hydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-3-hydride Roxytetrahydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl ) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxytetra hydro-2H-pyran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydride Roxytetrahydro-2H-pyran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl ) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxytetra hydro-2H-pyran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetra hydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydride Roxytetrahydro-2H-pyran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl ) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-3-hydroxyp peridin-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-3 -Hydroxypiperidin-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-3-hydride Roxypiperidin-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-3-hydride Roxypiperidin-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxyp peridin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H -pyran-2-carboxamide;
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydride Roxypiperidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide; or
(2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydride Roxypiperidin-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-2-carboxamide;
Or a pharmaceutically acceptable salt thereof. 제 1 항 내지 제 9 항 중 어느 한 항에 따른 화합물, 또는 이의 약학적으로 허용가능한 염, 및 약학적으로 허용가능한 담체를 포함하는 약학적 조성물.A pharmaceutical composition comprising the compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 제 1 항 내지 제 9 항 중 어느 한 항에 있어서, 약제로서 사용하기 위한 화합물, 또는 이의 약학적으로 허용가능한 염.The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, for use as a pharmaceutical. 제 1 항 내지 제 9 항 중 어느 한 항에 있어서, 기관의 섬유증; 간 질환 및 장애; 급성 신장 손상 및 만성 신장 질환; 심혈관 질환 및 장애; 간질성 폐 질환 및 장애; 세포 증식성 질환 및 암; 염증성 및 자가면역 질환 및 장애; 위장관 질환 및 장애; 췌장 질환 및 장애; 비정상적 혈관형성 관련 질환 및 장애; 뇌 관련 질환 및 장애; 신경병성 통증 및 말초 신경병증; 안구 질환 및 장애; 또는 이식 거부증의 예방 또는 치료에서 사용하기 위한 화합물, 또는 이의 약학적으로 허용가능한 염.The method according to any one of claims 1 to 9, comprising: fibrosis of the organ; liver disease and disorders; acute kidney injury and chronic kidney disease; cardiovascular diseases and disorders; interstitial lung diseases and disorders; cell proliferative diseases and cancer; Inflammatory and autoimmune diseases and disorders; Gastrointestinal diseases and disorders; pancreatic diseases and disorders; Diseases and disorders associated with abnormal angiogenesis; Brain-related diseases and disorders; Neuropathic pain and peripheral neuropathy; eye diseases and disorders; or a compound for use in the prevention or treatment of transplant rejection, or a pharmaceutically acceptable salt thereof. 기관의 섬유증; 간 질환 및 장애; 급성 신장 손상 및 만성 신장 질환; 심혈관 질환 및 장애; 간질성 폐 질환 및 장애; 세포 증식성 질환 및 암; 염증성 및 자가면역 질환 및 장애; 위장관 질환 및 장애; 췌장 질환 및 장애; 비정상적 혈관형성 관련 질환 및 장애; 뇌 관련 질환 및 장애; 신경병성 통증 및 말초 신경병증; 안구 질환 및 장애; 또는 이식 거부증의 예방 또는 치료를 위한 약제의 제조에 있어서의 제 1 항 내지 제 9 항 중 어느 한 항에 따른 화합물, 또는 이의 약학적으로 허용가능한 염의 용도.Fibrosis of organs; liver disease and disorders; acute kidney injury and chronic kidney disease; cardiovascular diseases and disorders; interstitial lung diseases and disorders; cell proliferative diseases and cancer; Inflammatory and autoimmune diseases and disorders; Gastrointestinal diseases and disorders; pancreatic diseases and disorders; Diseases and disorders associated with abnormal angiogenesis; Brain-related diseases and disorders; Neuropathic pain and peripheral neuropathy; eye diseases and disorders; or use of the compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the prevention or treatment of transplant rejection. 유효량의 제 1 항 내지 제 9 항 중 어느 한 항에 정의된 바와 같은 화합물, 또는 이의 약학적으로 허용가능한 염을 필요로 하는 대상체에게 투여하는 것을 포함하는, 기관의 섬유증; 간 질환 및 장애; 급성 신장 손상 및 만성 신장 질환; 심혈관 질환 및 장애; 간질성 폐 질환 및 장애; 세포 증식성 질환 및 암; 염증성 및 자가면역 질환 및 장애; 위장관 질환 및 장애; 췌장 질환 및 장애; 비정상적 혈관형성 관련 질환 및 장애; 뇌 관련 질환 및 장애; 신경병성 통증 및 말초 신경병증; 안구 질환 및 장애; 또는 이식 거부증의 방지 또는 치료 방법.Fibrosis of an organ, comprising administering to a subject in need an effective amount of a compound as defined in any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof; liver disease and disorders; acute kidney injury and chronic kidney disease; cardiovascular diseases and disorders; interstitial lung diseases and disorders; cell proliferative diseases and cancer; Inflammatory and autoimmune diseases and disorders; Gastrointestinal diseases and disorders; pancreatic diseases and disorders; Diseases and disorders associated with abnormal angiogenesis; Brain-related diseases and disorders; Neuropathic pain and peripheral neuropathy; eye diseases and disorders; or a method for preventing or treating transplant rejection.
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